Archive for the ‘Skin Stem Cells’ Category

Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitroin an in vitro fertilization clinicand then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body.

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells (hESCs) aregenerated by transferringcells from a preimplantation-stage embryointo a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. In the original protocol, the inner surface of the culture dish was coated with mouse embryonic skin cellsspecially treated so they will not divide. This coating layer of cells is called a feeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. Researchers have nowdevised ways to grow embryonic stem cells without mouse feeder cells. This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.

The process of generating an embryonic stem cell line is somewhat inefficient, so lines are not produced each time cells from the preimplantation-stage embryo are placed into a culture dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for six or more months without differentiating, are pluripotent, and appear genetically normal are referred to as an embryonic stem cell line. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

At various points during the process of generating embryonic stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them embryonic stem cells. This process is called characterization.

Scientists who study human embryonic stem cells have not yet agreed on a standard battery of tests that measure the cells' fundamental properties. However, laboratories that grow human embryonic stem cell lines use several kinds of tests, including:

As long as the embryonic stem cells in culture are grown under appropriate conditions, they can remain undifferentiated (unspecialized). But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. They can form muscle cells, nerve cells, and many other cell types. Although spontaneous differentiation is a good indication that a culture of embryonic stem cells is healthy, the process is uncontrolled and therefore an inefficient strategy to produce cultures of specific cell types.

So, to generate cultures of specific types of differentiated cellsheart muscle cells, blood cells, or nerve cells, for examplescientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. Through years of experimentation, scientists have established some basic protocols or "recipes" for the directed differentiation of embryonic stem cells into some specific cell types (Figure 1). (For additional examples of directed differentiation of embryonic stem cells, refer to the 2006 NIH stem cell report.)

Figure 1. Directed differentiation of mouse embryonic stem cells. Click here for larger image. ( 2008 Terese Winslow)

If scientists can reliably direct the differentiation of embryonic stem cells into specific cell types, they may be able to use the resulting, differentiated cells to treat certain diseases in the future. Diseases that might be treated by transplanting cells generated from human embryonic stem cells include diabetes, traumatic spinal cord injury, Duchenne's muscular dystrophy, heart disease, and vision and hearing loss.

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Excerpt from:
What are embryonic stem cells? [Stem Cell Information]

2009

"A UK and Canadian team have manipulated human skin cells to act like embryonic stem cells without using viruses making them safer for use in humans.

"Study leader Dr. Keisuke Kaji, from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said nobody, including himself, had thought it was really possible. 'It is a step towards the practical use of reprogrammed cells in medicine, perhaps even eliminating the need for human embryos as a source of stem cells,' he said."

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"'Ethical' stem cell creation hope," BBC News, March 1, 2009, http://news.bbc.co.uk/2/hi/health/7914976.stm

***

"A groundbreaking medical treatment that could dramatically enhance the body's ability to repair itself has been developed by a team of British researchers. The therapy, which makes the body release a flood of stem cells into the bloodstream, is designed to heal serious tissue damage caused by heart attacks and even repair broken bones.

"A possible danger with some other stem cell therapies in the pipeline is their use of embryonic stem cells. Because these can turn into any type of tissue, there is a risk they could grow into cancer cells when injected into patients. [This] treatment uses stem cells that can only grow into blood vessels, bone and cartilage, so the risk of causing cancer is removed."

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I. Sample, "Revolutionary stem cell therapy boosts body's ability to heal itself," The Guardian (United Kingdom) , January 8, 2009, http://www.guardian.co.uk/science/2009/jan/08/stem-cells-bone-marrow-heart-attack

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"Controversial research into the use of 'hybrid' human-animal embryos to make stem cells is in danger of stalling because of a lack of funding, British scientists claim.

"Since the furore broke scientists have developed a cheap and powerful new technique in which adult skin cells are reprogrammed to create cells that are almost identical to stem cells. Researchers have already used the technique to make so-called induced pluripotent stem (iPS) cells for patients with diabetes, muscular dystrophy and Down's syndrome.

[Quoting Harry Moore, head of reproductive biology at Sheffield University] 'What has happened is the field has moved on. You could argue that iPS cells are a more important area than hybrids now.' "

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I. Sample, "Rival stem cell technique takes the heat out of hybrid embryo debate," The Guardian. January 13, 2009, http://www.guardian.co.uk/science/2009/jan/13/hybrid-embryos-stem-cells

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"A dose of their own stem cells 'reset' the malfunctioning immune system of patients with early-stage multiple sclerosis and, for the first time, reversed their disability.

'This is the first study to actually show reversal of disability,' said Richard Burt, an associate professor in the division of immunotherapy at Northwestern, and the lead author of the study published yesterday in the British journal, the Lancet Neurology. 'Some people had complete disappearance of all symptoms.' "

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R. Waters, "Dose of Own Stem Cells Reverses Patients' Multiple Sclerosis," Bloomberg News, January 30, 2009, http://www.bloomberg.com/apps/news?pid=20601124&sid=akHXxf3bS3TY&refer=home

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"A new study suggests that adult bone marrow stem cells can be used in the construction of artificial skin. The findings mark an advancement in wound healing and may be used to pioneer a method of organ reconstruction."

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"Study Uses Bone Marrow Stem Cells to Regenerate Skin," Physorg, January 14, 2009, http://www.physorg.com/news151166956.html

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2008

"The reality is that the bulk of today's stem-cell research relies on adult stem cells taken from bone marrow, blood, skeletal muscles, body fat and umbilical cord blood. Scientists have even managed to coax adult skin cells to mimic the versatility of embryonic stem cells, which can grow virtually any cell or tissue in the human body. Unlike embryonic stem cells, though, these adult stem cells are being tested in humans right now, with very real possibilities to change the way various diseases are treated in the next five to 10 years."

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T. Wheeler, "Stem cells mature," Beacon Journal (Akron, Ohio), April 6, 2008.

***

"For the first time, scientists at Children's Hospital of Pittsburgh of UPMC have discovered a unique population of adult stem cells derived from human muscle that could be used to treat muscle injuries and diseases such as heart attack and muscular dystrophy.

"Because this is an autologous transplant, meaning from the patient to himself, there is not the risk of rejection you would have if you took the stem cells from another source

"Myoendothelial cells also showed no propensity to form tumors, a concern with other stem cell therapies."

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"Pittsburgh scientists identify human source of stem cells with potential to repair muscle damaged by disease or injury," Children's Hospital of Pittsburgh, September 4, 2007, http://www.pslgroup.com/dg/28732E.htm.

***

2007

"An Ecuadorian stem cellexpert said on September 24 that transplants of autologous adult bone marrow stem cells restored some function in spinal cord injury (SCI) patients who have been paralyzed for an average of four years, some up to 22 years.

"Of the 25 patients who provided more than three months and up to 14 months follow up: 15 gained the ability to stand up, 10 could walk on the parallels with braces, seven could walk without braces and five could walk with crutches. Three patients recovered full bladder control, and 10 patients regained some form of sexual function. No adverse events or abnormal reactions to implantation were observed.

'By implanting an adult's own bone marrow stem cells, we've seen significant improvements in the quality of life for those who suffer from spinal cord injuries,' said Francisco Silva, executive vice president of research and development for PrimeCell Therapeutics."

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"Marrow Stem Cell Transplants Restore Spinal Cord Functions," Stem Cell Business News, Sept. 24, 2007, http://www.stemcellresearchnews.com/absolutenm/anmviewer.asp?a=867&z=15

***

"In recent years, scientists have discovered that red bone marrow is the body's Swiss Army repair kit. It contains a traveling laboratory of cells that can heal the liver, heart, kidneys, leg arteries, pancreas, and even ovaries and the brain. Up to 40 percent of the liver can be regrown from stem cells found in bone marrow, researchers at New York University School of Medicine, Yale University School of Medicine and Sloan-Kettering Cancer Center found."

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B. J. Fikes, "Body parts Bone marrow: The body's repair kit," North County Times (San Diego, CA), May 20, 2006, http://www.nctimes.com/lifestyles/health-med-fit/article_0bcace84-44ac-51bc-99a0-b1bf6ddb6d21.html

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2006

"The results of a study published in the April issue of Stem Cells and Development suggest that human stem cells derived from bone marrow are predisposed to develop into a variety of nerve cell types, supporting the promise of developing stem cell-based therapies to treat neurodegenerative disorders such as Parkinson's disease and multiple sclerosis.

"When transplanted into the central nervous system, [these cells] will develop into a variety of functional neural cell types, making them a potent resource for cell-based therapy."

--

"New Findings Support Promise of Using Stem Cells to Treat Neurodegenerative Diseases," Business Wire, May 1, 2006, http://findarticles.com/p/articles/mi_m0EIN/is_2006_May_1/ai_n16135565/

2005

"A team of Texas and British researchers says it has produced large amounts of embryoniclike stem cells from umbilical cord blood, potentially ending the ethical debate affecting stem-cell research -- the need to kill human embryos. The international researchers said the cells -- called cord-blood-derived-embryoniclike stem cells, or CBEs -- have the ability to turn into any kind of body tissue, like embryonic stem cells do, and can be mass-produced using technology derived from NASA.... "Scientists believe the ability to replicate tissue could lead to the development of ways to replace organs as well as treat life-threatening diseases such as diabetes, Alzheimer's and Parkinson's, which have been the focus of stem-cell research." -- J. Price, "Advance made in stem-cell debate," The Washington Times, August 20, 2005, http://www.washingtontimes.com/national/20050820-122747-2417r.htm

* * *

"Various studies that have been conducted around the world, including a limited number performed in the United States, have suggested that when patients with heart failure receive stem cells taken from their bone marrow, their hearts show signs of improved function and recovery." -- "Stem Cells With Heart Bypass Surgery Trial To Begin At University Of Pittsburgh," ScienceDaily, August 25, 2005, http://www.sciencedaily.com/releases/2005/08/050825070117.htm

* * * "Researchers in Boston have isolated a kind of cell from human bone marrow that they say has all the medical potential of human embryonic stem cells.... "Tufts University researchers used specialized cell-sorting machines to pluck the peculiar cells from samples of bone marrow obtained from different donors. Tests suggested the cells are capable of morphing into many, and perhaps all, of the various kinds of cells that make up the human body. ...

"When a batch of the newly identified marrow cells were injected into the hearts of rats that had experienced heart attacks, some of the cells turned into new heart muscle while others became new blood vessels to support the ailing hearts. ...

"'I think embryonic stem cells are going to fade in the rearview mirror of adult stem cells,' said Douglas W. Losordo, the Tufts cardiologist who left the effort.... Bone marrow, he said, 'is like a repair kit. Nature provided us with these tools to repair organ damage.'"

-Rick Weiss, "Marrow Has Cells Like Stem Cells, Tests Show," Washington Post, Feburary 2, 2005, p. A3, at http://www.washingtonpost.com/wp-dyn/articles/A55369-2005Feb1.html .

* * * "[Erica] Nader, 26, of Farmington Hills, Mich., was the first American to travel to Portugal, in March 2003, for experimental sugery for spinal cord injury. She was injured in July 2001 in an auto accident... She was paralyzed from the top of her arms down. "In the procedure...a team of doctors opened Nader's spinal cord to clear out any scar tissue.... Then, using a long tube, they took a sample of olfactory mucosal cells from the ridge of her nose.... These cells are among the body's richest supply of adult stem cells and are capable of becoming any type of cell, depending on where they are implanted. In this case, these adult stem cells were to take on the job of neurons, or nerve cells, once implanted in the spinal cord at the site of an injury. ... "And after three years, magnetic imaging resonance tests show that the cells indeed promote the development of new blood cells and synapses, or connections between nerve cells, says Dr. Carlos Lima, chief of the Lisbon team. ... "Dr. Pratas Vital, one of two neurosurgeons on the team, calls the transplanted cells spinal cord autografts, a term that indicates the cells come from a person's own body, not fetal or embryonic stem cells. ...

"[Erica] is much stronger and much more capable of lifting her arms, bending her knees on a slanted exercise board and standing erect. ... Once, she was paralyzed from her biceps down. Now, she can push herself off an exercise ball, do arm lifts and help raise herself off a floor mat. ... In the past six weeks, she's started to walk in leg braces with a walker or on a treadmill." -Patricia Anstett, "Paraplegic improving after stem-cell implant," The Indianapolis Star, January 16, 2005, at http://www.indystar.com/articles/5/209449-5235-047.html.

* * * 2004

"[E]vidence from three different labs the University of Minnesota, the Robert Wood Johnson Medical School in New Jersey, and Argonne National Laboratory outside Chicago have found three different ASCs [adult stem cells] that may be completely plastic. ... As the team leader at the Robert Wood Johnson School, Ira Black, told me, 'In aggregate, our study and various others do support the idea that one [adult stem cell] can give rise to all types of tissue.' ...

-Michael Fumento, "The Adult Answer," National Review Online, December 20, 2004, at http://www.nationalreview.com/comment/fumento200412200902.asp.

* * * "Scientists have transplanted adult stem cells from the bone marrow of rats into the brains of rat embryos and found that thousands of the cells survive into adulthood, raising the possibility that someday developmental abnormalities could be prevented or treated in the womb. "Dr. Ira Black, chairman of the department of neuroscience at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, said the cells took on the properties of brain cells, migrating to specific regions and taking up characteristics of neighboring cells. ... "Black and his colleagues used a specific type of bone marrow cell called a stromal cell, taken from the leg bones of adult rats. 'We see this potentially as an appropriate treatment for prenatal disease, mental retardation and congenital conditions,' Black said. The hope is that a patient's own bone barrow might someday be the source for replacing brain cells lost to illness and brain trauma, experts say, eliminating the need to use human embryonic stem cells. "In a separate study, Dr. Alexander Storch of the University of Ulm, Germany, recently took bone marrow and stromal cells from six healthy people and converted the cells into immature neural stem cells. ... 'A single cell culture could grow all major brain cell types,' said Storch, who used specific growth factors to help them differentiate. ...Storch is now transplanting the cells into mice with multiple sclerosis, Parkinson's disease and stroke symptoms. In the stroke study, the labeled adult stromal cells migrated to the area surrounding the stroke damage, he said. They had all of the chemical, electrical and functional properties of brain cells." -Jamie Talan, "Stem cell transplant a success," Newsday, May 12, 2004, at http://www.mult-sclerosis.org/news/May2004/SuccessfulRatStemCellTransplant.html.

* * * "'Cord blood stem cells have the same capacity to cure disease as do embryonic stem cells, as they can become any cell in the body...,' said Dr. William Schmidt, Jr., an oncologist with the Charleston Cancer Center in N. Charleston, SC. "'The use of umbilical cord blood stem cells in the treatment of disease is one of the most prominent advancements in medicine today. Developments in this field will revolutionize medicine and disease treatment,' said Dr. [Roger] Markwald [Professor and Chair of the Department of Cell Biology and Anatomy at the Medical University of South Carolina]."

-Press Release, "CureSource Issues Statement on Umbilical Cord Blood Stem Cells vs. Embryonic Stem Cells," May 12, 2004, at http://home.businesswire.com/portal/site/altavista/index.jsp?ndmViewId=news_view&newsId=20040512005909&newsLang=en.

* * * "California scientists have found that neural stem cells can target and track deadly brain tumor cells. ...The discovery by researchers at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute in Los Angeles means that neural stem cells may someday be effective 'delivery systems' to transport cancer-killing gene and immune products. ... "'We have previously demonstrated the uncanny ability of neural stem cells to seek out and destroy satellites of tumor cells in the brain,' said John S. Yu, senior author of the study and co-director of the Comprehensive Brain Tumor Program a Cedars-Sinai. '...With this knowledge, we hope to expedite the translation of this powerful and novel strategy for the clinical benefit of patients with brain tumors.'" -Press release, "Neural stem cells may help fight cancer," May 5, 2004, at http://www.nlm.nih.gov/medlineplus/news/fullstory_17570.html. * * * "'We're not trying to change the [adult stem] cells in any way before we put them in the body. These are very early precursor cells. They have the potential to become almost anything, and they adapt quickly once they're inside,' said [Tulane University Center for Gene Therapy research professor Dr. Brian] Butcher. Tests on rats with damaged spines have shown that cell growth occurs in the spine [after adult stem cell injection] and allows the animals to walk again. ... "Using adult stem cells sidesteps some of the legal and ethical issues involved in using fetal...or embryonic stem cells.... And there may be other benefits as well. 'We're not against stem-cell research of any kind,' said Butcher. 'But we think there are advantages to using adult stem cells. For example, with embryonic stem cells, a significant number become cancer cells, so the cure could be worse than the disease. And they can be very difficult to grow, while adult stem cells are very easy to grow.' "But perhaps the biggest advantage to adult stem cells is that they sidestep immunological concerns because the cells used to treat a patient come from his or her own body."

-Heather Heilman, "Great Transformations," The Tulanian, Spring 2004, at http://www2.tulane.edu/article_news_details.cfm?ArticleID=5155.

* * * "Had a major heart attack? In the not-too-distant future, doctors may be able to use stem cells to regenerate damaged heart muscle. And here's the exciting part: They can do it using stem cells that aren't extracted from human embryos. "[G]iven the controversy over harvesting cells from embryos, doctors have been exploring other possibilities. The payoff: A team from the University of Texas M.D. Anderson Cancer Center in Houston recently repaired heart muscles in animals by injecting them with stem cells extracted from human blood. It's the stem-cell equivalent of Columbus reaching America: Not only would cells harvested from one's own body eliminate the risk that they would be rejected, but obtaining them would be a simple, painless proposition. "'This work gives us a way to get the cells that's as easy as giving a blood sample,' says Edward Yeh, M.D., lead author of the study. The real mind boggler is what the stem cells might mean to the 1.2 million Americans who suffer heart attacks each year." -Special Report, "Good news about bad things that happen to your parents," USA Weekend magazine, March 5-7, 2004, p. 6, at http://www.usaweekend.com/04_issues/040307/040307aging.html#heart. * * * 2003

"Scientists in Canada have turned adult skin cells into the building blocks of brain cells --opening the way for their use in new therapies for such incurable diseases. The discovery, by a team at the University of Toronto, is particularly exciting as it promises to provide a readily accessible and ethically neutral source of neural stem cells -- the precursors of nerve and brain tissue. "While other groups have managed to create these cells before, they have generally required the use of adult stem cells from bone marrow, which are difficult and painful to extract, or embryonic stem cells, which require the destruction of a human embryo. "If the Toronto technique is perfected for clinical use it would allow neural stem cells to be made from a patient's skin, ensuring a perfect genetic match that would not be rejected by the body. The cells would then be transplanted into the brains of people with neurological disorders, to replace, for example, the specialized dopamine neurons that are lost in Parkinson's disease." -Oliver Wright, "Patients' Own Skin Cells Turned into Potential Alzheimer's Treatment," The Times (London), December 10, 2003, Home News, p. 8.

* * * "Massachusetts General Hospital researchers have harnessed newly discovered cells from an unexpected source, the spleen, to cure juvenile diabetes in mice, a surprising breakthrough that could soon be tested in local patients and open a new chapter in diabetes research... "'This shows there might be a whole new type of therapy that we haven't tapped into,' said Dr. Denise Faustman, MGH immunology lab director and lead author of the new study, which appears today in the journal Science. 'We've figured out how to regrow an adult organ'." -R. Mishra, "Juvenile diabetes cured in lab mice," The Boston Globe, November 14, 2003, p. A2. * * * "There is now an emerging recognition that the adult mammalian brain, including that of primates and humans, harbours stem cell populations suggesting the existence of a previously unrecognised neural plasticity to the mature CNS [central nervous system], and thereby raising the possibility of promoting endogenous neural reconstruction... Since large numbers of stem cells can be generated efficiently in culture, they may obviate some of the technical and ethical limitations associated with the use of fresh (primary) embryonic neural tissue in current transplantation strategies." -T. Ostenfeld and C. Svendsen, "Recent advances in stem cell neurobiology," Advances and Technical Standards in Neurosurgery, vol. 28 (2003), p. 3. * * * "Stem cells in our bone marrow usually develop into blood cells, replenishing our blood system. However, in states of emergency, the destiny of some of these stem cells may change: They can become virtually any type of cell liver cells, muscle cells, nerve cells responding to the body's needs. Prof. Tsvee Lapidot and Dr. Orit Kollet of the Weizmann Institute's Immunology Department have found how the liver, when damaged, sends a cry for help to these stem cells. 'When the liver becomes damaged, it signals to stem cells in the bone marrow, which rush to it and help in its repair as liver cells,' says Lapidot...

"The findings could lead to new insights into organ repair and transplants, especially liver-related ones. They may also uncover a whole new stock of stem cells that can under certain conditions become liver cells. Until a few years ago only embryonic stem cells were thought to possess such capabilities. Understanding how stem cells in the bone marrow turn into liver cells could one day be a great boon to liver repair as well as an alternative to the use of embryonic stem cells." -"Weizmann Institute scientists find that stem cells in the bone marrow become liver cells," EurakAlert, August 11, 2003, at http://www.eurekalert.org/pub_releases/2003-08/wi-wis_1081103.php.

* * * I.S. Abuljadayel, Chief Scientific Officer of Tri-Stem Inc., on his study published in the July 2003 Current Medical Research and Opinion on producing pluripotent stem cells from adult blood cells:

"This new technology offers a viable option for the generation of large numbers of pluripotent stem cells. These are likely to have many clinical and research applications. The source material is blood, the most accessible tissue in our body which can be extracted by simple venipuncture or aphaeresis. The procedure raises no ethical concerns and removes the need to resort to embryos or aborted fetuses. The technology is also cost-effective, donor-friendly producing relatively large quantities of stem cells within a short time, which could eventually save patient lives and shorten patient waiting lists." -"Stem cell-like plasticity induced in mature mononuclear cells," Reuters Health, July 7, 2003.

* * * "This is an example of promising experimental therapies involving stem cells from bone marrow. Until just a few years ago, conventional wisdom held that only embryonic stem cells could turn into any cell in the body. But that thinking began to change as studies showed that stem cells from bone marrow could become heart, muscle, nerve, or liver cells. Now, the results of clinical trials conducted in Britain, Germany and Brazil show that heart patients injected with their own bone marrow cells benefit from the treatment."

-N. Touchette,"Bone Marrow Stem Cells Heal the Heart," Genome News Network, May 2, 2003, at http://www.genomenewsnetwork.org/articles/05_03/sc_heart.shtml * * * "Stem cells from bone marrow can transform into insulin-producing cells, scientists have shown, suggesting a future cure for diabetes... "Transplants of pancreatic cells have been tried between people, but the supplies are restricted and recipients have to take strong anti-rejection medication. Embryonic stem cells have also been converted into insulin-producing cells, but also produce immune-rejection, in addition to ethical concerns. But taking bone marrow cells from a patient, developing them into beta cells and then reimplanting them would have none of these difficulties. Also, much of the technology for bone marrow transplantation is already well developed, says study leader Mehboob Hussain, at the New York University School of Medicine. "'I am absolutely excited by the potential applications of our findings,' he said. 'In our body, there is an additional, easily available source of cells that are capable of becoming insulin-producing cells.'" -S. Bhattacharya, "Bone marrow experiments suggest diabetes cure," NewScientist.com News Service, March 17, 2003, at http://www.newscientist.com/news/news.jsp?id=ns99993508. * * * 2002

"The use of human embryonic stem cells has been confronted with major obstacles because of bio-ethical and political issues involved obtaining them, as well as the suggestion that embryonic stem cells may lack appropriate developmental instructions, making them potentially less feasible for engrafting into adult tissue... "As compared to embryonic stem cells, adult derived stem cells are endowed with additional developmental instructions and may be better suited for therapeutic purposes. According to [Dr. Shahin Rafii of Cornell University Medical College], 'We are approaching a day when a patient's own stem cells can be induced to divide and develop into tissue that can replace that which is diseased or destroyed, making overcrowded organ transplant lists and rejection of foreign tissues a thing of the past'." -"Mechanism For Regulation Of Adult Stem Cells Found," UniSci - Daily University Science News, May 31, 2002, at http://unisci.com/stories/20022/0531021.htm * * * On the versatility of adult hematopoietic (blood-producing) stem cells, HSCs: "[R]ecent studies have suggested that a subpopulation of HSCs may have the ability to contribute to diverse cell types such as hepatocytes, myocytes, and neuronal cells, especially following induced tissue damage... These surprising findings contradict the dogma that adult stem cells are developmentally restricted." -K. Bunting and R. Hawley, "The tao of hematopoietic stem cells: toward a unified theory of tissue regeneration," Scientific World Journal, April 10, 2002, p. 983.

* * * 2001

Commenting on a study by researchers at New York University, Yale and Johns Hopkins: "'There is a cell in the bone marrow that can serve as the stem cell for most, if not all, of the organs in the body,' says Neil Theise, M.D., Associate Professor of Pathology at NYU School of Medicine... '(t)his study provides the strongest evidence yet that the adult body harbors stem cells that are as flexible as embryonic stem cells'." -"Researchers Discover the Ultimate Adult Stem Cell," ScienceDaily Magazine, May 4, 2001, at http://www.sciencedaily.com/releases/2001/05/010504082859.htm * * * "Umbilical cords discarded after birth may offer a vast new source of repair material for fixing brains damaged by strokes and other ills, free of the ethical concerns surrounding the use of fetal tissue, researchers said Sunday."

Excerpt from:
Scientific Experts Agree Embryonic Stem Cells Are ...

As we age, our stem cells lose their potency. Your skin's ability to repair itself just isn't what it used to be. The result can be fine lines, wrinkles, age spots, and sagging skin. But non-embryonic stem cells -- the same stem cells active early in life -- are highly potent. Lifeline stem cell serums tap into the potency of these stem cells to help renew your skin's appearance.

Scientists at Lifeline Skin Care discovered that human non-embryonic stem cell extracts can help fight the look of fine lines, wrinkles and age spots. These stem cell extracts are mixed with powerful moisturizers and other carefully selected ingredients to help slow the signs of aging. And Lifeline stem cell serums were born.

The first types of human stem cells to be studied by researchers were embryonic stem cells, donated from in vitro fertilization labs. But because creating embryonic stem cells involves the destruction of a fertilized human embryo, many people have ethical concerns about the use of such cells.

Lifeline Skin Care (through its parent company, International Stem Cell Corporation) is the first company in the world to discover how to create human non-embryonic stem cells -- and how to take extracts from them. As a result, you need never be concerned that a viable human embryo was damaged or destroyed to create these extraordinary skin care products.

The non-embryonic stem cells in Lifeline stem cell serums are derived from unfertilized human oocytes (eggs) which are donated to ISCO from in vitro fertilization labs and clinics.

Lifeline Skin Care's exclusive skin care products are a combination of several discoveries and unique high-technology, with patent-pending formulations.

Original post:
Stem Cell Serums Visibly Renew Skin / Lifeline Skin Care Blog

Int J Biomater. 2012; 2012: 926059.

1Department of Surgery, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA

2Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University, 257 Campus Drive, Stanford, CA 94305, USA

3Department of Surgery, Plastic and Reconstructive Surgery Division, Division of Burn Surgery, University of Michigan Health Systems, 1500 East Medical Center Drive, Ann Arbor, MI 48104, USA

4The Biomaterials and Advanced Drug Delivery (BioADD) Laboratory, Stanford University, 300 Pasteur Drive, Grant Building, Room S380, Stanford, CA 94305, USA

Academic Editor: Kadriye Tuzlakoglu

Received 2012 Jan 15; Accepted 2012 Apr 8.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Stem cell-based therapies offer tremendous potential for skin regeneration following injury and disease. Functional stem cell units have been described throughout all layers of human skin and the collective physical and chemical microenvironmental cues that enable this regenerative potential are known as the stem cell niche. Stem cells in the hair follicle bulge, interfollicular epidermis, dermal papillae, and perivascular space have been closely investigated as model systems for niche-driven regeneration. These studies suggest that stem cell strategies for skin engineering must consider the intricate molecular and biologic features of these niches. Innovative biomaterial systems that successfully recapitulate these microenvironments will facilitate progenitor cell-mediated skin repair and regeneration.

Skin serves as the interface with the external world and maintains key homeostatic functions throughout life. This regenerative process is often overlooked until a significant exogenous and/or physiologic insult disrupts our ability to maintain skin homeostasis [1]. Complications of normal repair often result in chronic wounds, excessive scarring, or even malignant transformation, cutaneous diseases that contribute substantially to the global health burden [2, 3]. As human populations prone to inadequate healing (such as the aged, obese, and diabetics) continue to expand, novel therapies to treat dysfunctional skin repair and regeneration will become more critical.

Tissue regeneration has been demonstrated in multiple invertebrate and vertebrate species [4]. In humans, even complex tissues can regenerate without any permanent sequelae, such as liver, nerves, and skin. Although the typical result after significant organ injury is the formation of scar, regeneration after extensive skin and soft tissue trauma has been reported, most notably after digit tip amputation [5]. It is well accepted that human skin maintains the ability to regenerate; the question for researchers and clinicians is how to harness this potential to treat cutaneous injury and disease.

The integumentary system is a highly complex and dynamic system composed of myriad cell types and matrix components. Numerous stem cell populations have been identified in skin and current research indicates that these cells play a vital role in skin development, repair, and homeostasis [1, 6, 7]. In general, stem cells are defined by their ability to self-renew and their capacity to differentiate into function-specific daughter cells. These progenitor cells have been isolated from all skin layers (epidermis, dermis, hypodermis) and have unique yet complimentary roles in maintaining skin integrity. The promise of regenerative medicine lies in the ability to understand and regulate these stem cell populations to promote skin regeneration [4].

Wound healing is a highly regulated process that is thought to be mediated in part by stem cells [8, 9]. This has prompted researchers to examine the use of stem cells to augment skin repair following injury. Preclinical studies have suggested that the secretion of paracrine factors is the major mechanism by which stem cells enhance repair [10, 11]. Consistent with this hypothesis, conditioned media from mesenchymal stem cells (MSCs) have been shown to promote wound healing via activation of host cells [11, 12]. Clinical studies have suggested that topical delivery of MSCs may improve chronic wound healing [1315] and multiple groups have demonstrated the benefit of using recombinant cytokines (many of which are known to be secreted by stem cells) in patients with recalcitrant wounds [16]. However, more research is needed to determine the mechanisms by which stem cell therapies might improve wound healing in humans.

For example, the extent of stem cell engraftment and differentiation following topical delivery remains unclear. In one study, bone-marrow-derived allogeneic MSCs injected into cutaneous wounds in mice were shown to express keratinocyte-specific proteins and contributed to the formation of glandular structures after injury [17]. Although long-term engraftment was poor (only 2.5% of MSCs remained engrafted after four weeks), levels of secreted proangiogenic factors were greater in MSC-treated wounds. Our laboratory has demonstrated that local injection of allogeneic MSCs improved early wound closure in mice but that injected MSCs contributed to less than 1% of total wound cells after four weeks [18]. Taken together, these studies suggest that the benefits observed with stem cell injections are the result of early cytokine release rather than long-term engraftment and differentiation.

One potential reason for the transient presence of exogenous stem cells is the absence of proper contextual cues after cells are delivered into the wound. The dynamic microenvironment, or niche, of stem cells is responsible for regulating their stem-like behavior throughout life [19, 20]. This niche is comprised of adjacent cells (stem and nonstem cells), signaling molecules, matrix architecture, physical forces, oxygen tension, and other environmental factors (). A useful analogy is the seed versus soil paradigm in which seeds (stem cells) will only thrive in the proper chemical and physical soil environment (wound bed) [4]. Clearly, we need to better define what these niches are and how they dictate cell behavior to fully realize the potential of progenitor cell therapies.

Potential components of the skin stem cell niche. Features common to skin stem cell niches include dynamic regulation of matrix ligands, intercellular interactions, and biochemical gradients in the appropriate three-dimensional contexts. Engineered biomaterials ...

The epidermis is comprised of at least three major stem cell populations: the hair follicle bulge, the sebaceous gland, and the basal layer of interfollicular epithelium [21]. Because these subpopulations are responsible for regulating epithelial stratification, hair folliculogenesis, and wound repair throughout life [22], the epidermis has become a model system to study regeneration. Elegant lineage tracing and gene mapping experiments have elucidated key programs in epidermal homeostasis. Specifically, components of the wingless-type (Wnt)/-catenin, sonic hedgehog (Shh), and transforming growth factor (TGF)-/bone morphogenetic protein (BMP) pathways appear to be particularly relevant to epidermal stem cell function [1, 22, 23]. Microarray analyses have even indicated that hair follicle stem cells share some of the same transcriptomes as other tissue-specific stem cells [24], suggesting that conserved molecular machinery may control how environmental stimuli regulate the stem cell niche [25].

Epithelial stem cells from the bulge, sebaceous gland, and basal epithelium have common features, including expression of K5, K14, and p63, and their intimate association with an underlying basement membrane (BM) [26]. These cells reside in the basal layer of stratified epithelium and exit their niche during differentiation [26]. This process is mediated in part by BM components such as laminin and cell surface transmembrane integrins that control cell polarity, anchorage, proliferation, survival, and motility [27, 28]. Epithelial progenitor cells are also characterized by elevated expression of E-cadherin in adherens junctions and reduced levels of desmosomes [29], underscoring the importance of both extracellular and intercellular cues in stem cell biology.

In addition to complex intraepithelial networks, signals from the dermis (e.g., periodic expression of BMP2 and BMP4) are thought to regulate epithelial processes [30]. Dermal-derived stem cells may even differentiate into functional epidermal melanocytes [31], suggesting that mesenchymal-epithelial transitions may underlie skin homeostasis, as has been shown in hepatic stem cells [32]. Recently, it has been demonstrated that irreversibly committed progeny from an epithelial stem cell lineage may be recycled and contribute back to the regenerative niche [33], further highlighting the complexity of the epidermal regeneration.

In contrast to the highly cellular nature of the epidermis, the dermis is composed of a heterogeneous matrix of collagens, elastins, and glycosaminoglycans interspersed with cells of various embryonic origin. Recent studies suggest that a cell population within the dermal papilla of hair follicles may function as adult dermal stem cells. This dermal unit contains at least three unique populations of progenitor cells differentiated by the type of hair follicle produced and the expression of the transcription factor Sox2 [34]. Sox2-expressing cells are associated with Wnt, BMP, and fibroblast growth factor (FGF) signaling whereas Sox2-negative cells utilize Shh, insulin growth factor (IGF), Notch, and integrin pathways [35, 36]. Skin-derived precursor (SKP) cells have also been isolated from dermal papillae and can be differentiated into adipocytes, smooth myocytes, and neurons in vitro [37, 38]. These cells are thought to originate in part from the neural crest and have been shown to exit the dermal papilla niche and contribute to cutaneous repair [39].

Researchers have also demonstrated that perivascular sites in the dermis may act as an MSC-like niche in human scalp skin [40]. These perivascular cells express both NG2 (a pericyte marker) and CD34 (an MSC and hematopoietic stem cell marker) and are predominantly located around hair follicles. Perivascular MSC-like cells have been shown to protect their local matrix microenvironment via tissue-inhibitor-of-metalloproteinase (TIMP-) mediated inhibition of matrix metalloproteinase (MMP) pathways, suggesting the importance of the extracellular matrix (ECM) niche in stem cell function [41]. Interestingly, even fibroblasts have been shown to maintain multilineage potential in vitro and may play important roles in skin regeneration that have yet to be discovered [42, 43].

The ability to harvest progenitor cells from adipose tissues is highly appealing due to its relative availability (obesity epidemic in the developed world) and ease of harvest (lipoaspiration). Secreted cytokines from adipose-derived stem cells (ASCs) have been shown to promote fibroblast migration during wound healing and to upregulate VEGF-related neovascularization in animal models [44]. ASCs have even been harvested from human burn wounds and shown to engraft into cutaneous wounds in a rat model [45]. Although these multipotent cells have only been relatively recently identified, they exhibit significant potential for numerous applications in skin repair [46].

ASCs are often isolated from the stromal vascular fraction (SVF) of homogenized fat tissue. These multipotent cells are closely associated with perivascular cells and maintain the potential to differentiate into smooth muscle, endothelium, adipose tissue, cartilage, and bone [47, 48]. Researchers have attempted to recreate the ASC niche using fibrin matrix organ culture systems to sustain adipose tissue [49]. Using this in vitro system, multipotent stem cells were isolated from the interstitium between adipocytes and endothelium, consistent with the current hypothesis that ASCs derive from a perivascular niche.

Detailed immunohistological studies have demonstrated that stem cell markers (e.g., STRO-1, Wnt5a, SSEA1) are differentially expressed in capillaries, arterioles, and arteries within adipose tissue, suggesting that ASCs may actually be vascular stem cells at diverse stages of differentiation [50]. Adipogenic and angiogenic pathways appear to be concomitantly regulated and adipocytes secrete multiple cytokines that induce blood vessel formation including vascular endothelial-derived growth factor (VEGF), FGF2, BMP2, and MMPs [51, 52]. Additionally, cell surface expression of platelet-derived growth factor receptor (PDGFR) has been linked to these putative mural stem cells [53]. Reciprocal crosstalk between endothelial cells and ASCs may regulate blood vessel formation [54] and immature adipocytes have been shown to control hair follicle stem cell activity through PDGF signaling [55]. Taken together, these studies indicate that the ASC niche is intimately associated with follicular and vascular homeostasis but further studies are needed to precisely define its role in skin homeostasis [48].

Strategies to recapitulate the complex microenvironments of stem cells are essential to maximize their therapeutic potential. Biomaterial-based approaches can precisely regulate the spatial and temporal cues that define a functional niche [56]. Sophisticated fabrication and bioengineering techniques have allowed researchers to generate complex three-dimensional environments to regulate stem cell fate. As the physicochemical gradients, matrix components, and surrounding cells constituting stem cell niches in skin are further elucidated (), tissue engineered systems will need to be increasingly scalable, tunable, and modifiable to mimic these dynamic microenvironments [5761]. A detailed discussion of different biomaterial techniques for tissue engineering is beyond the scope of this paper, but we refer to reader to several excellent papers on the topic [6270].

Skin-specific stem cells and putative features of their niche.

One matrix component thought to regulate interactions between hair follicle stem cells and melanocyte stem cells is the hemidesmosomal collagen XVII [71]. Collagen XVII controls their physical interactions and maintains the self-renewal capacity of hair follicles via TGF-, indicating that biomaterial scaffolds containing collagen XVII may be necessary for stem cell-mediated hair follicle therapies. Another matrix component implicated in the hair follicle niche is nephronectin, a protein deposited into the underlying basement membrane by bulge stem cells to regulate cell adhesion via 81 integrins [72]. Hyaluronic acid fibers have been incorporated into collagen hydrogels to promote epidermal organization following keratinocyte seeding [73], and in vitro studies have demonstrated the critical role of collagen IV in promoting normal epithelial architecture when keratinocytes are grown on fibroblast-populated dermal matrices [74]. These studies collectively suggest that tissue engineered matrices for skin regeneration will need to recapitulate the complex BM-ECM interactions that define niche biology [75].

The role of MSCs in engineering skin equivalents has been studied using either cell-based or collagen-based dermal equivalents as the scaffolding environment [76]. When these constructs were grown with keratinocytes in vitro, only the collagen-based MSCs promoted normal epidermal and dermal structure, leading the authors to emphasize the necessity of an instructive biomaterial-based scaffold to direct stem cell differentiation, proliferation, paracrine activity [and] ECM deposition [76]. Our laboratory has reported that MSCs seeded into dermal-patterned hydrogels maintain greater expression of the stem cell transcription factors Oct4, Sox2, and Klf4 as compared to those grown on two-dimensional surfaces [18]. MSCs seeded into these niche-like scaffolds also exhibited superior angiogenic properties compared to injected cells [18], indicating that stem cell efficacy may be enhanced with biomaterial strategies to recapitulate the niche. Another study demonstrated that ASC delivery in natural-based scaffolds (dermis or small intestine submucosa) resulted in improved wound healing compared to gelatin-based scaffolds, suggesting the importance of biologically accurate architecture for stem cell delivery [77].

Researchers have developed novel three-dimensional microfluidic devices to study perivascular stem cell niches in vitro [78]. For example, MSCs seeded with endothelial cells in fibrin gels were able to induce neovessel formation within microfluidic chambers through 61 integrin and laminin-based interactions. Fibrin-based gels have also been used to study ASC and endothelial cell interactions in organ culture [49] and to control ASC differentiation in the absence of exogenous growth factors, demonstrating the importance of the three-dimensional matrix environment in regulating the ASC niche [79]. These studies indicate that the therapeutic use of ASCs in skin repair will likely be enhanced with biomaterial systems that optimize these cell-cell and cell-matrix contacts.

Finally, it must be recognized that the wound environment is exceedingly harsh and often characterized by inflammation, high bacterial loads, disrupted matrix, and/or poor vascularity. In this context, it should not be surprising that injection of naked stem cells into this toxic environment does not produce durable therapeutic benefits. Our laboratory has shown that the high oxidative stress conditions of ischemic wounds can be attenuated with oxygen radical-quenching biomaterial scaffolds that also deliver stem cells [80]. Other researchers have shown that oxygen tension, pH levels, and even wound electric fields may influence stem cell biology, suggesting that the future development of novel sensor devices will allow even finer control of chemical microgradients within engineered niches [70, 81]. It is also important to acknowledge that current research on niche biology has been performed largely in culture systems or rodent models, findings that will need to be rigorously confirmed in human tissues before clinical use.

As interdisciplinary fields such as material science, computer modeling, molecular biology, chemical engineering, and nanotechnology coordinate their efforts, multifaceted biomaterials will undoubtedly be able to better replicate tissue-specific niche environments. Recent studies suggest that the cells necessary for skin regeneration are locally derived [5], indicating that adult resident cells alone may have the ability to recreate skin (). Thus, the ability to engineer the proper environment for skin stem cells truly has the potential to enable regenerative outcomes. We believe that next-generation biomaterial scaffolds will not only passively deliver stem cells but also must actively modify the physicochemical milieu to create a therapeutic niche.

Locally derived skin stem cells may harbor the potential to regenerate skin. Stem cells populations have been identified in various niches throughout the skin, including the epidermal stem cell in the hair follicle bulge, sebaceous glands, and interfollicular ...

Current research indicates that skin regeneration is highly dependent upon interactions between resident progenitor cells and their niche. These microenvironmental cues dictate stem cell function in both health and disease states. Early progress has been made in elucidating skin compartment-specific niches but a detailed understanding of their molecular and structural biology remains incomplete. Biomaterials will continue to play a central role in regenerative medicine by providing the framework upon which to reconstruct functional niches. Future challenges include the characterization and recapitulation of these dynamic environments using engineered constructs to maximize the therapeutic potential of stem cells.

Articles from International Journal of Biomaterials are provided here courtesy of Hindawi Publishing Corporation

Originally posted here:
Stem Cell Niches for Skin Regeneration

Stem Cell Technology represents a major breakthrough in anti-aging and regenerative skin care, by protecting, strengthening, and replenishing our own human skin cells. Where Peptides stimulate different functions acting as messengers to skin cells, stem cell technology improves the life of the core of the cell. Working in synergy with peptides, they enhance the effectiveness of peptides and other active ingredients.

Antiaging effects - The stem cells in our skin have a limited life expectancy due to DNA damage, aging and oxidative stress. As our own skin stem cells age, they become more difficult to repair and replenish. Protection of our stem cells becomes more and more beneficial as our skin ages, and with the advent of stem cells, we are now able to delay the natural aging process even further than before.

Expected benefits of stem cells technology for regenerative skin care:

Stem Cell Replenishing Serum Featuring a potent concentration of apple and edelweiss plant stem cells, state-of-the-art peptides, and other cutting edge ingredients, the Stem Cell Replenishing Serum is thoroughly formulated to produce age defying results, restoring the youthful look and vitality to aging skin.

Stem Cell Moisturizing Cream Also featuring a healthy concentration of apple and edelweiss plant stem cells, peptides, and numerous botanical extracts, the Stem Cell Moisturizing Cream is formulated to produce age defying results while also helping to maintain healthy and youthful looking skin as a daily moisturizer.

Our Stem Cell Applications:

LPAR Stem Cell Products contain a wide variety of stem cells with healthy and potent concentrations in order to deliver the results skin care consumers strive for. The first stem cell ingredient discovered and produced is a liposomal preparation based on the stem cells of a rare Swiss apple. The revolutionary active ingredient, Malus Domestica by PhytoCellTec is based on a high tech plant cell culture technology. It has been proven to protect the longevity of skin stem cells and provide significant anti-wrinkle effects. Since the discovery and the worldwide success of Apple Stem Cells introduction to the cosmetic and skin care marketplace, other new and exciting stem cell ingredients have been discovered to provide extraordinary results for all skin types.

We were proud to be the first skin care line to offer the ground-breaking combination of Apple and Edelweiss stem cells, and are dedicated to formulating the best new and existing stem cell ingredients into our product line as the technology continues to develop.

To inquire about purchasing LPAR Stem Cell products. visit our Retail Locator page.

Featuring a luxurious and potent blend of three major botanical stem cells (Apple, Gardenia Jasminoides, Echinacea Angustifolia) two state-of-the-art peptides (Nutripeptides, Matrixyl synthe6), and numerous botanical extracts and minerals, the Stem Cell Nourishing Mask is thoroughly formulated to nourish, firm, and energize mature skin. Total Stem Cell Concentration: 5.5% - Total Peptide Concentration: 9.0%

Directions: Using fingertips, apply on clean, dry skin twice weekly. Avoid the eye area. The mask can be left on the skin for prolonged periods (during the day or overnight). Allow at least 10-15 minutes for the mask to penetrate the skin before rinsing with water or applying additional product For external use only.

Ingredients: Water (Aqua), Glycerin, Glyceryl Acrylate/Acrylic Acid Copolymer, Hydrolyzed Rice Protein (Nutripeptides), Sodium Hyaluronate, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38 (Matrixyl synthe6), Biosaccharide Gum-1, Olea Europaea (Olive) Fruit Oil, Gardenia Jasminoides Meristem Cell Culture, Xanthan Gum, Malus Domestica Fruit Cell Culture, Lecithin, Porphyridium Polysaccharide, Echinacea Angustifolia Meristem Cell Culture, Carbomer, Triethanolamine, Mentha Pipertita (Peppermint) Extract, Camellia Sinensis (Green Tea) Leaf Extract, Palmaria Palmata (Dulce) Extract, Chamomilla Recutita (Matricaria) Flower Extract, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Copper PCA, Zinc PCA, Dipotassium Glycyrrhizate, Olea Europaea (Olive) Fruit Extract, Aloe Barbadensis Leaf Juice Powder, Fragrance (Parfum)

Featuring a plant and fruit stem cell enhanced blend of three major stem cells (Apple, Edelweiss, Alpine Rose), state-of-the-art peptides (Eyeseryl, Nutripeptides), the Stem Cell Eye Therapy is an advanced eye formula designed to nourish, firm, and increase skin elasticity and skin smoothness around the eye area. Total Stem Cell Concentration: 6.75% - Total Peptide Concentration: 11.0%

Directions: Using fingertips, apply product around both eyes on clean, dry skin once or twice daily before applying a moisturizer or night cream. For external use only.

Ingredients: Water, Acetyl Tetrapeptide-5 (Eyeseryl), Sodium Hyaluronate, Hydrolyzed Rice Protein (Nutripeptides), Glycerin, Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Xanthan Gum, Malus Domestica Fruit Cell Culture (Apple Stem Cells), Lecithin, Porphyridium Polysaccharide, Camellia Sinensis (Green Tea) Leaf Extract, Cucumis Sativus (Cucumber) Fruit Extract, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Carbomer, Triethanolamine, Rhododendron Ferrugineum Leaf Cell Culture Extract (Alpine Rose Stem Cells) Isomalt, Sodium Benzoate, Lactic Acid, Sodium Polystyrene Sulfonate, Allantoin, Copper PCA, Aloe Barbadensis Leaf Juice Powder

Plant stem cells represent a major breakthrough in skin care, launching the beginning of a new system of treating the skin...by protecting and replenishing the building blocks of what makes up our own skin: Stem Cells. Rather than working around the natural aging process of our skin stem cells, we now have the technology available to improve the life of our skins most important and central component.

Featuring a potent combination of apple, edelweiss, and grape stem cells, state-of-the-art peptides, and other cutting edge ingredients, the Stem Cell Replenishing Serum is thoroughly formulated to produce age defying results, restoring the youthful look and vitality to aging skin.

Directions: Apply with fingertips on clean, dry skin once or twice daily. Avoid the eye area by approximately 1 cm. Suitable for mature skin types. For external use only.

Ingredients: Water (Aqua), Glycerin, Dipeptide Diaminobutyroyl Benzylamide Diacetate, Acetyl Octapeptide-3, Malus Domestica Fruit Cell Culture (Apple Stem Cells), Hydrolyzed Ceratonia Siliqua Seed Extract, Palmitoyl Tripeptide-5, PEG-8 Dimethicone, Saccharide Isomerate, Imperata Cylindrica (Root) Extract, Polysorbate 20, Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Leucojum Aestivum Bulb Extract, Triethanolamine, Carbomer, Xanthan Gum, Vitis Vinifera Fruit Cell Extract (Grape Stem Cells), Isomalt, Sodium Benzoate, Lecithin, Disodium EDTA, Allantoin, Aloe Barbadensis Leaf Juice Powder, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, PEG-8-Carbomer, Fragrance (Parfum)

Plant stem cells represent a major breakthrough in skin care, launching the beginning of a new system of treating the skin...by protecting and replenishing the building blocks of what makes up our own skin: Stem Cells. Rather than working around the natural aging process of our skin stem cells, we now have the technology available to improve the life of our skins most important and central component.

Featuring a healthy concentration and a diverse group of stem cells (apple, edelweiss, grape), peptides, and numerous botanical extracts, the Stem Cell Moisturizing Cream is formulated to produce age-defying results, while also helping to maintain healthy and youthful looking skin as a daily moisturizer.

Directions: For mature skin and/or skin conditioning, apply onto clean, dry skin with fingertips once daily. Avoid the eye. For external use only.

Ingredient Highlights: Plant/Fruit Stem Cells 4% - Malus Domestica (Apple Stem Cells) - Leontopodium Alpinum Cell Culture Extract (Edelweiss Stem Cells) - Vitis Vinifera Fruit Cell Extract (Grape Stem Cells)

Ingredients: Water (Aqua), Glycerin, Isopropyl Myristate, Caprylic/Capric Triglyceride, Cetearyl Olivate, Sorbitan Olivate, Sorbitol, Saccharide Isomerate, Sodium Hyaluronate, Leucojum Aestivum Bulb Extract, Malus Domestica Fruit Cell Extract (Apple Stem Cells), Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Vitis Vinifera Fruit Cell Extract (Grape Stem Cells), Crambe Abyssinica Seed Oil, Dimethicone, Cetyl Alcohol, Imperata Cylindrica (Root) Extract, Acetyl Octapeptide-3 (SNAP-8), Dipeptide Diaminobutyroyl Benzylamide Diacetate(SYN-AKE), Palmitoyl Tripeptide-3 (SYN-COL), Hydrolyzed Ceratonia Siliqua Seed Extract, Aloe Barbadensis Leaf Juice Powder, Olea Europaea (Olive) Leaf Extract, Glyceryl Stearate, Xantham Gum, Cetyl Palmitate, Sorbitan Palmitate, Bisabolol, Tocopheryl Acetate, Fragrance, Phenoxyethanol, Caprylyl Glycol, Ethylhexyglycerin, Hexylene Glycol, PEG-8, Carbomer, Lecithin, Isomalt, Sodium Benzoate, Disodium EDTA

[ pH: 5.00 ]

Featuring high concentrations of Vitamin C (Tetrahexyldecyl Ascorbate), Orange Stem Cells, and Peptides, this is a multi-beneficial cream with state-of-the-art actives formulated to deliver significant and lasting results.

Tetrahexyldecyl Ascorbate is a stable, oil soluble form of Vitamin C that penetrates deeper into the skin than traditional ascorbic acid based Vitamin C. It's a proven skin lightener, a powerful Anti-Oxidant, DNA protector, and increases collagen synthesis more effectively than ascorbic acid. Orange Stem Cells work to increase elasticity and skin resistance to the dermis, which increase firmness and diminish wrinkles while also working synergistically with peptides to further increase skin elasticity and collagen support.

How to Use: Smooth a pearl sized drop onto the face once daily (morning or evening). Avoid the eye area while applying. Follow with Solar Protection if used during the day.

Ingredients: Water (Aqua), Tetrahexyldecyl Ascorbate (Vitamin C Ester), Glycerin, Hexyl Laurate, Caprylic/Capric Triglyceride, Butylene Glycol, Sorbitol, Stearic Acid, Glyceryl Stearate, PEG-100 Stearate, Cetyl Alcohol, Sorbitan Stearate, Polysorbate 60, Acetyl Hexapeptide-8, Sodium Hyaluronate, Squalane, Dimethicone, PPG-12/SMDI Copolymer, Citrus Aurantium Dulcis Callus Culture Extract (Orange Stem Cells), Tocopheryl Acetate, Cetearyl Ethylhexanoate, Linoleic Acid, Glycine Soja (Soybean) Sterols, Phospholipids, Di-PPG-2 Myreth-10 Adipate, Retinol, Polysorbate 20, Hydrolyzed Glycosaminoglycans, Alcohol, Ectoin, Lecithin, Cyclotetrapeptide-24 Aminocyclohexane Carboxylate, Glucosamine HCl, Algae Extract, Yeast Extract, Urea, Micrococcus Lysate, Plankton Extract, Arabidopsis Thaliana Extract, Magnesium Aluminum Silicate, Xanthan Gum, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Disodium EDTA, Citrus Aurantium Dulcis (Orange) Peel Oil

[ pH: 4.7 ]

The Vitamin C Stem Cell Mask combines a potent blend of Vitamin C Ester (Tetrahexyldecyl Ascorbate), highly concentrated plant and fruit stem cells (Argan, Sea Fennel), and Aldenine, a unique peptide that acts as a cellular detoxifier and a collagen III booster.

Directions: Apply on clean, dry skin. Avoid the eye area. The mask may be left on the skin (i.e. during the day or overnight), or it may be rinsed off with lukewarm water after 10 - 15 minutes. Suitable for mature skin types.

Ingredients: Water (Aqua), Tetrahexyldecyl Ascorbate, Kaolin, Glycerin, Glyceryl Stearate, Sorbitan Olivate, Cetearyl Olivate, Cetyl Palmitate, Sorbitol, Sorbitan Palmitate, Stearic Acid, Caprylic/Capric Triglyceride, Cyclopentasiloxane, Cyclhexasiloxane, Carthamus Tinctorius (Safflower) Seed Oil, Punica Granatum Extract, Butylene Glycol, Ananas Sativus (Pineapple) Fruit Extract, Carica Papaya Fruit Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-1, Argania Spinosa (Argan Stem Cells) Sprout Cell Extract, Crithmum Maritimum (Sea Fennel Stem Cells) Callus Culture Filtrate, Oligopeptide-68, Sodium Oleate, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Polyacrylamide, C13-14 Isoparaffin, Laureth-7, Isomalt, Hydrogenated Lecithin, Lecithin, Sodium Benzoate, Allantoin, Citrus Aurantium Dulcis (Orange) Peel Oil, Magnesium Aluminum Silicate, Xanthan Gum, Disodium EDTA

[ pH: 6.00 ]

Originally designed to prepare and increase the skins receptiveness to our Professional Peptide Peel, the Premier Peptide Serum has gone on to become our most powerful anti-wrinkle product for year-round home care due to its high concentration and diversity of peptides. Composed of a total concentration of 65% peptides, the Premier Peptide Serum is a state of the art facial serum expertly formulated to reduce the signs of aging, energizing mature skin.

The Intensive Clarifying Peptide Cream is a unique and high potency moisturizing cream formulated with an abundance of natural skin lighteners, peptides, and botanical extracts that combine to clarify and firm mature skin, while effectively minimizing fine lines and wrinkles.

The Collagen Peptide Complex builds off of our original Collagen Copper Activating Complex, and includes an advanced formulation of peptides, including Syn-Coll, a small but powerful peptide that stimulates collagen synthesis at a cellular level, helping to compensate for any collagen deficit in the skin.

Boasting a remarkable collection of natural and innovative ingredients from exotic plants and enhanced peptides, the neck firming cream has been designed & tested to firm and energize mature skin, while providing increased smoothness and elasticity to the often neglected neck area.

Providing sufficient hydration is the most essential way to keep our skin healthy and youthful. While many of our products assist in hydrating the skin, hydration is the main focus of the Nano-Peptide B5 Complex, acting as the foundation for your home care regimen. Fortified with Sodium Hyaluronate (30%) and Pantothenic acid, it provides an especially deep and complete hydration. Because of the presence of peptides, it also assists in tightening and firming the skin while allowing for maximum absorption and effectiveness.

Designed for mature skin, this sophisticated moisturizer promotes cell renewal, stimulating the dermis layer of the skin with a high potency blend of peptides (Argireline, Matrixyl, & Biopeptide-CLTM) and botanical extracts that make it a particularly refined and effective moisturizing cream for age management.

The A&M Eye Recovery Therapy is an advanced age management treatment, applying the most tried and true peptides and delivery systems; Argireline & Matrixyl, to the highly wrinkle prone and fragile eye area, providing diminished wrinkle depth, and increased firmness and elasticity. The peptide Eyeliss is added to further enhance this treatment by counteracting skin slackening, puffiness, and decreasing irritation.

The A&M Facial Recovery Therapy is an advanced age-management treatment that blends the most tried and true peptides and delivery systems; Argireline & Matrixyl. Stimulating the deeper layers of the skin, the A&M Facial Recovery Therapy provides diminished wrinkle depth, as well as an increase in skin elasticity and firmness.

Originally designed to prepare and increase the skins receptiveness to our Professional Peptide Peel, the Premier Peptide Serum has gone on to become our most powerful anti-wrinkle product for year-round home care due to its high concentration and diversity of peptides. Composed of a total concentration of 65% peptides, the Premier Peptide Serum is a state of the art facial serum expertly formulated to reduce the signs of aging, energizing mature skin.

Directions: For mature skin types; apply at least three weeks before beginning the Lucrece Professional Peptide Peel treatment, and use twice a day leading up to the Peel. For year round application, apply once per day after the Collagen Peptide Complex. Avoid the eye area by at least 1 cm during application.

Peptides: SYN-AKE: A small peptide (Dipeptide Diaminobutyroyl Benzylamide Diacetate) that mimics the activity of Waglerin 1, a polypeptide that is found in the venom of the Temple Viper, Tropidolaemus wagleri. Clinical trials have shown SYN-AKE is capable of reducing wrinkle depth by inhibiting muscle contractions. SNAP-8: An anti-wrinkle (Acetyl Octapeptide-3) elongation of the famous Hexapeptide Argireline. The study of the basic biochemical mechanisms of anti-wrinkle activity led to the revolutionary Hexapeptide which has taken the cosmetic world by storm. ARGIRELINE: (Acetyl Hexapeptide-8) MATRIXYL: (Palmitoyl Pentapeptide-4) REGU-AGE: (Hydrolyzed Rice Bran Protein - Oxido Reductases - Soybean Protein) BIOPEPTIDE CL: (Palmitoyl Oligopeptide) RIGIN: (Palmitoyl Tetrapeptide-7) EYELISS: (Dipeptide-2 & Palmitoyl Tetrapeptide-7) INYLINE: (Acetyl Hexapeptide 30)

Other Ingredients: Water, Sodium Hyaluronate, Spiraea Ulmaria Flower Extract & Centella Asiatica Extract & Echinacea Purpurea Extract, Phenoxyethanol & Benzyl Alcohol & Potassium Sorbate & Tocopherol, Meadowsweet, Hydrocotyl Extract, Leucojum Aestivum Bulb Extract, Amino Acids, Diazolidinyl Urea, Imperata Cylindrica Extract, SMDI Copolymer, Hydroxyethylcellulose

[ pH: 5.00 ]

This unique and high potency moisturizing cream is formulated with an abundance of natural skin lighteners, peptides, and botanical extracts that combine to help clarify and energize mature skin.

Directions: Smooth a pearl size drop onto the face, gently massaging in with fingertips once per day (morning), avoiding the eye area. Follow with solar protection if applicable.

Skin Lightening Agents: Mulberry Bark, Saxifrage Extract, Grape Extract, Scutellaria Root Extracts, Vitamin C Ester (Tetrahexyldecyl Ascorbate), Emblica Fruit Extract, Licorice Root Extract.

Ingredients: Water (Aqua), Saxifrage Extract & Grape Extract & Butylene Glycol & Water & Mulberry Bark Extract & Scutellaria Root Extract, Prunus Amygdalus Dulcis (Sweet Almond) Oil, Caprylic/Capric Triglycerides, Sesamum Indicum (Sesame) Seed Oil, Cetearyl Olivate & Sorbitan Olivate, Glycerin, Palmitoyl Pentapeptide-4 (Matrixyl), Tetrahexyldecyl Ascorbate (C-Ester), Glyceryl Stearate & PEG 100 Stearate, Stearic Acid, Theobroma Cocao (Cocoa) Seed Butter, PPG-12/SMDI Copolymer, Butyrospermum Parkii (Shea) Butter, Tocopheryl Acetate (Vitamin E), Phyllanthus Emblica Fruit Extract, Palmitoyl Tripeptide-5 (Syn-Coll), Triethanolamine, Phenoxyethanol, Mangifera Indica (Mango) Seed Butter, Darutoside, Tricholoma Matsutake Singer (Mushroom) Extract, Imperata Cylindrica (Root) Extract, Fragrance (Parfum), Glucosamine HCL & Algae Extract & Yeast Extract & Urea, Retinyl Palmitate (Vitamin A), Centella Asiatica Extract & Echinacea Purpurea Extract, Xanthan Gum, Arctostaphylos Uva Ursi Leaf Extract, Glycyrrhiza Glabra Root Extract, Magnesium Aluminum Silicate, Disodium EDTA

[ pH: 5.75 ]

Specializing in firming the skin, the Collagen Peptide Complex builds off of our original Collagen Copper Activating Complex, and adds a combination of (5) major peptides, helping to keep the skin looking its youngest and most alive, as it works to firm, and add elasticity & texture to the skin. For best results, apply directly after the Nano-Peptide B5 Complex.

Directions: Apply a liberal amount on clean, dry face using fingertips, and massage into the skin. Let dry, and follow with a moisturizer and sun-block if used during the day, or the Vitamin A Facial Cream + III if used at night. Warning: For mature skin only. If redness occurs, lessen use to once or twice per week. If reactions persist, discontinue use.

Ingredients: Water (Aqua), Dipalmitoylhydroxyproline, Glycerin, Palmitoyl Tetrapeptide-7 (Rigin), Palmitoyl Oligopeptide (Biopeptide-CL), Butylene Glycol, Yeast (Faex Extract), Hydrocotyl Extract & Coneflower Extract, Aloe Barbadensis Leaf Extract, Palmitoyl Tripeptide-5 (Syn-Coll), Acetyl Hexapeptide-8 (Argireline), Palmitoyl Pentapeptide-4 (Matrixyl), Panthenol, Phenoxyethanol & Caprylyl Glycol & Ethylhexylglycerin & Hexylene Glycol, Triethanolamine, Carbomer, Decarboxy Carsonine HCI, Citrus Grandis (Grapefruit) Seed Extract, Copper PCA, Olea Europaea (Olive) Leaf Extract, Disodium EDTA

[ pH: 5.50 ]

Boasting a remarkable collection of natural and innovative ingredients from exotic plants and enhanced peptides, the neck firming cream has been designed & tested to firm and energize mature skin, while providing increased smoothness and elasticity to the often neglected neck area.

Directions: On clean dry skin, apply onto the neck area with fingertips in an upward motion. Apply twice a day, or as needed.

Key Ingredients: Bio-Bustyl: Stimulates cell metabolism, promotes collagen synthesis, and enhances fibroblast (collagen-producing cell) proliferation. INCI: Glyceryl Polymethacrylate, Soy Protein Ferment, PEG-8, & Palmitoyl Oligopeptide Polylift: Using a cross-linking technology, biopolymerization, Polylift reinforces the natural lifting effect of sweet almond proteins, providing a smooth firmness & radiance to the surface of the skin. INCI: Prunus Amygdalus Dulcis (Sweet Almond) Seed Extract.

Ingredients: Deionized Water, Prunus Amygdalus Dulcis (Sweet Almond Oil), Caprylic/Capric Triglycerides, Sesamum Indicum (Sesame) Seed Oil, Simmondsia (Jojoba) Seed Oil/ Buxus Chinensis, Cetearyl Alcohol, Dicetyl Phosphate, Ceteth-10 Phosphate, Palmitoyl Oligopeptide, Palmitoyl Tetrapeptide-7, Prunus Amygdalus Dulcis Seed Extract, Terminalia Catappa Leaf Extract & Sambucus Nigra Flower Extract & PVP & Tannic Acid, Glyceryl Polymethacrylate & Rahnella/ Soy Protein Ferment & PEG-8 & Palmitoyl Oligopeptide, Glycerin, Glyceryl Stearate & PEG 100 Stearate, Biosaccharide Gim-1, PPG-12/ SMDI Copolymer, Phyllanthus Emblica Fruit Extract, Stearic Acid, Centella Asiatica Extract & Darutosidetriethanolamine, Tocopheryl Acetate, Magnifera Indica (Mango) Seed Butter, Glycerin & Aqua & Lysolecithin & Perilla Frutescens Seed Oil, Xantham Gum, Retinyl Palmitate, Tetrahexyldecyl Ascorbate (Vitamin C Ester), Echinacea Purpurea Extract, Imperata Cylindrica (Root) Extract, Glycyrrhiza Glabra Root Extract, Magnesium, Aluminum Silicate, Disodium EDTA

[ pH: 6.25 ]

Hydration is the most essential way to keep our skin healthy feeling and healthy looking. While many of our products assist in hydrating the skin, hydration is the main focus for this product, making it an essential for all skin types. Fortified with Hyaluronic (30%) and Panthenol (Vitamin B5), the Nano-Peptide B5 Complex provides an especially deep and complete hydration. With the addition of peptides, it also assists in tightening and firming the skin while allowing for maximum absorption and effectiveness.

The Nano-Peptide B5 Complex should be applied directly after cleansing the skin, as the 2nd step in skin care regimens for all skin types (morning & night). For best results, age management regimens should follow with the Stem Cell Replenishing Serum and/or the Collagen Peptide Complex before moisturizing.

Directions: Apply a healthy amount on clean, dry skin. May be used around the eye area.

Key Ingredients: Palmitoyl Pentapeptide-4: Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of the dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines. Acetyl Hexapeptide-8: Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin). Hyaluronic Acid (30%): Penetrates deep into the skin, providing ample moisture Panthenol: Enhances formation of skin pigments for younger looking skin, and contains deep penetrating properties that allow a more complete hydration.

Other Ingredients: Water (Aqua), Hyaluronic Acid, Panthenol (Vitamin B5), MDI Complex, Palmitoyl Pentapeptide-4, Acetyl Hexapeptide-8, Phenoxyethanol, Hydrolyzed Wheat Protein, Butylene Glycol, Hydrocotyl & Coneflower Extract, Glycosaminoglycans.

[ pH: 5.5 ]

Designed for mature, sun damaged, and/or dehydrated skin, the Anti-Wrinkle Facial Cream is a peptide enriched moisturizer focused on increasing skin firmness & elasticity, and fortifying the skin with anti-oxidants & botanical extracts to facilitate healthy feeling and healthy looking skin.

Directions: Smooth a pearl size drop onto the face, massage into skin thoroughly. For use in the morning (recommended), follow with solar protection.

Ingredients: Water (Aqua), Glycerin, Dimethicone, Caprylic/Capric Triglycerides, C12-15 Alkyl Benzoate, Linoleic Acid & Glycine Soja (Soybean) Sterols & Phospholipids, Acetyl Hexapeptide-8, Butylene Glycol & Carbomer & Polysorbate 20 & Palmitoyl Pentapeptide-4, Cetearyl Alcohol & Dicetyl Phosphate & Ceteth-10 Phosphate, Glyceryl Stearate & PEG 100 Stearate, PPG-12/ SMDI Copolymer, Phyllanthus Emblica Fruit Extract, Darutoside, Cocoa Butter, Cetyl Alcohol, Butyrospermum Parkii (Shea Butter), Saccharomyces/Xylinum Black Tea Ferment & Glycerin & Hydroxyethylcellulose, Glucoseamine HCL & Algae Extract & Saccharomyces Cerevisiae (Yeast Extract) & Urea, Steareth-20 & Palmitoyl Tetrapeptide-7, Centella Asiatica Extract & Echinacea Purpurea Extract, Hydrolyzed Vegetable Protein, Imperata Cylindrica (Root) Extract & PEG-8 & Carbomer, Phenoxyethanol & Caprylyl Glycol & Ethylhexylglycerin & Hexylene Glycol, Polyglyceryl Methacrylate & Propylene Glycol & Palmitoyl Oligopeptide, Cyclopentasiloxane & Dimethicone, Stearic Acid, Mangifera Indica (Mango) Seed Butter, Tocopheryl Acetate, Glycyrrhiza Glabra Root Extract, Arctostaphylos Uva Ursi Leaf Extract, Chlorella Vulgaris Extract, Corallina Officinalis Extract, Dipotassium Glycyrrhizate, PEG-8 & Tocopherol & Ascorbyl Palmitate & Ascorbic Acid & Citric Acid, Disodium EDTA, Magnesium Aluminum Silicate, Xanthan Gum, Triethanolamine, Retinyl Palmitate, Lavandula Angustifolia (Lavender) Oil

[ pH: 5.75 ]

This advanced eye care treatment is expertly formulated to diminish the depth, increase firmness & elasticity, and to counteract skin slackening to the highly wrinkle prone and fragile eye area. Featuring (4) major peptides (Argireline, Matrixyl, Eyeliss, & Regu-age), the A&M Eye Recovery Therapy is our most potent eye treatment, and is recommended for mature skin.

Directions: Using fingertips, massage to surrounding eye areas affected by wrinkles due to muscle contractions. Also use in the nasal labial area. For best results, apply once per evening, followed by the A&M Facial Recovery Therapy, and/or the Vitamin A Facial Cream + III.

Ingredients Highlights: Palmitoyl Pentapeptide-4 (Matrixyl): Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines of the skin. Acetyl Hexapeptide-8 (Argireline): Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin). Dipeptide-2 & Palmitoyl Tetrapeptide-7 (Eyeliss): Combats the effect of tiredness and hypertension, as well as the natural effects of aging, which contribute to the formation of bags under the eyes, Eyeliss is an outstanding anti-aging ingredient. Soy Peptides & Hydrolyzed Rice Bran Extract (Regu-Age): A highly active complex of specially purified soy and rice peptides and biotechnologically derived yeast protein, Regu-Age effectively addresses dark circles and puffiness around the eyes.

Other Ingredients: Water, Sodium Hyaluronate, Centella Asiatica Extract & Echinacea Purpurea Extract, Xanthan Gum-Chondrus Crispus & Glucose, Lecithin & Dipalmitoyl Hydroxyproline, Imperata Cylindrica Extract, PEG-8 Dimethicone, Cyclomethicone

[ pH: 6.25 ]

An advanced age management treatment that blends the most tried and true peptides and delivery systems, Argireline & Matrixyl, helping to prevent skin aging induced by repeated facial movement caused by excessive catecholamine release. Stimulating the deeper layers of the skin, the A&M Facial Recovery Therapy provides diminished wrinkle depth, as well as an increase in the elasticity and firmness of the skin. Recommend for mature skin types.

Directions: Using fingertips apply to facial areas and massage into skin once per evening, allowing it to absorb into the skin. Apply directly after the A&M Eye Recovery Therapy.

Ingredients Highlights: Palmitoyl Pentapeptide-4: Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines of the skin. Acetyl Hexapeptide-8: Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin).

Other Ingredients: Deionized Water, Sodium Hyaluronate, Lecithin & Dipalmitoyl Hydroxyproline, Hydrocotyl & Coneflower Extracts, Glycosaminoglycans, Glucosamine HCI & Alagae Extract & Yeast Extract & Urea, Magnesium Ascorbyl Phosphate, Glycine HCL, Retinyl Palmitate

[ pH: 6.25 ]

Addressing the multiple problems of sun and age damaged skin, the Intensive Clarifying Facial Cream + III is a glycolic acid based moisturizer featuring three potent skin lighteners; Kojic Acid, Licorice, and Hydro- quinone (2%), which quickly & effectively treat hyperpigmentation & discolorations.

Vitamin C Ester (Tetrahexyldecyl Ascorbate) is a stable, oil-soluble form of Vitamin C, providing high level skin lightening, enhanced collagen synthesis, and increased DNA & UV protection with higher absorption capabilities and less irritating than Ascorbic Acid.

Because of how well it protects the skins collagen fibers, ascorbic acid based Vitamin C is widely considered one of the most effective antioxidants for skin rejuvenation & revitalization. The 20% Vitamin C Lightening drops combine a potent concentration of ascorbic acid with aloe, green tea leaf extract, and mushroom extract. *Also available is our original Vitamin C Serum, containing a milder blend of ascorbic acid (14%).

The Anti-Wrinkle Eye Cream contains a high potency blend of peptides, including EyelissTM & Regu-age (in addition to Argireline & Matrixyl) which work synergistically to improve firmness, elasticity, and reduce puffiness & dark circles around the eye area.

Addressing the multiple problems of sun and age damaged skin, the Intensive Clarifying Facial Cream + III moisturizer combines three powerful lightening. Agents: Hydroquinone, Kojic Acid, & Licorice, with Alpha Lipoic Acid, Vitamin C, & Co-enzyme Q10, minimizing fine lines, evening skin tone, and naturally exfoliating the outer layer of the skin while providing a 15 sun protection factor (SPF).

Directions: Smooth a pearl sized drop onto the face once or twice daily. Avoid eye area. If used during the day, apply additional sun protection if skin is in contact with the sun for an extended period (twenty minutes or more).

Active Ingredients: Octyl Methoxycinnamate - 7.5% Octyl Salcylate - 5% Glycolic Acid - 4% Benzophenone - 3% Hydroquinone - 2%

Inactive Ingredients: Deionized Water, Glyceryl Stearate & PEG-100 Stearate, Ascorbic Acid (Vitamin C), Alpha Lipoic Acid, Co-enzyme Q 10, Kojic Acid, Cetyl Alcohol, Licorice, Palmitic Acid, Octyl Salcylate, Phenoxyethanol, Tocopheryl Acetate, Essential Oil of Rosewood, Disodium tEDTA

[ pH: 4.5 ]

Vitamin C Ester is a stable, oil-soluble form of Vitamin C, providing high level Skin Lightening, enhanced Collagen Synthesis, and increased DNA & UV protection with higher absorption capabilities than Ascorbic Acid.

Directions: On clean, dry skin, apply four to five drops directly onto the face once a day, avoiding the eye area.

Ingredients: Cyclomethicone, Tetrahexyldecyl Ascorbate (Vitamin C Ester 10%), PPG-12/SMDI Copolymer, Santalum Album Extract, Phellodendrone Amurense Bark Extract, Barley Extract, Jojoba Seed Oil/Buxus Chinensis, Tocopheryl Acetate, Phenoxyethanol, Tricholoma Matsutake Singer (Mushroom Extract), Ascorbyl Palmitate, Bisabolol

[ pH: 7.0 ]

Ascorbic acid based Vitamin C is widely considered one of the most effective antioxidants for rejuvenating mature skin due to its ability to protect the skins collagen fibers, and for its ability to help inhibit melanin production, creating a lightening effect to the skin. The 20% Vitamin C Lightening Drops combine a potent concentration of ascorbic acid with aloe, green tea extract, and an exotic mushroom extract (Tricholoma Matsutake Singer) for additional lightening.

Directions: On clean, dry skin apply four to five drops directly onto the face once daily. Avoid the eye area. Thoroughly wash hands after use. Though a light tingling sensation is normal, if irritation (redness) results after application, discontinue or reduce the frequency of use of the product.

Ingredients: Water (Aqua), Ascorbic Acid -20%, Ethoxydiglycol, Hydroxyethylcellulose, Phenoxyethanol, Polysorbate 20, Camellia Sinensis Leaf Extract, Aloe Barbadensis Leaf Extract, Mushroom Extract (Tricholoma Matsutake Singer)-Enzymes- Alcohol, Sodium Sulfite, Disodium EDTA

[ pH: 3.00 ]

The Anti-Wrinkle Eye Cream is formulated to reduce puffiness, enhances firmness, strengthens connective tissues, and to help diminish dark circles around the eye area. In contrast to the A&M Eye Recovery Therapy, the Anti-Wrinkle Eye Cream concentrates on the upper layers of the skin, making it a great day moisturizer for the eyes.

Directions: Apply around the eye area with the ring finger once daily. For best results, follow with a moisturizer and solar protection.

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anti-aging stem cells - innovative treatments for skin ...

Skin is the soft outer covering of vertebrates. Other animal coverings, such as the arthropod exoskeleton have different developmental origin, structure and chemical composition. The adjective cutaneous means "of the skin" (from Latin cutis, skin). In mammals, the skin is an organ of the integumentary system made up of multiple layers of ectodermal tissue, and guards the underlying muscles, bones, ligaments and internal organs.[1] Skin of a different nature exists in amphibians, reptiles, and birds.[2] All mammals have some hair on their skin, even marine mammals like whales, dolphins, and porpoises which appear to be hairless. The skin interfaces with the environment and is the first line of defense from external factors. For example, the skin plays a key role in protecting the body against pathogens[3] and excessive water loss.[4] Its other functions are insulation, temperature regulation, sensation, and the production of vitamin D folates. Severely damaged skin may heal by forming scar tissue. This is sometimes discoloured and depigmented. The thickness of skin also varies from location to location on an organism. In humans for example, the skin located under the eyes and around the eyelids is the thinnest skin in the body at 0.5mm thick, and is one of the first areas to show signs of aging such as "crows feet" and wrinkles. The skin on the palms and the soles of the feet is 4mm thick and the back is 14mm thick and is the thickest skin in the body. The speed and quality of wound healing in skin is promoted by the reception of estrogen.[5][6][7]

Fur is dense hair.[8] Primarily, fur augments the insulation the skin provides but can also serve as a secondary sexual characteristic or as camouflage. On some animals, the skin is very hard and thick, and can be processed to create leather. Reptiles and fish have hard protective scales on their skin for protection, and birds have hard feathers, all made of tough -keratins. Amphibian skin is not a strong barrier, especially regarding the passage of chemicals via skin and is often subject to osmosis and diffusive forces. For example, a frog sitting in an anesthetic solution would be sedated quickly, as the chemical diffuses through its skin. Amphibian skin plays key roles in everyday survival and their ability to exploit a wide range of habitats and ecological conditions.[9]

Mammalian skin is composed of two primary layers:

The epidermis is composed of the outermost layers of the skin. It forms a protective barrier over the body's surface, responsible for keeping water in the body and preventing pathogens from entering, and is a stratified squamous epithelium,[10] composed of proliferating basal and differentiated suprabasal keratinocytes. The epidermis also helps the skin regulate body temperature.[citation needed]

Keratinocytes are the major cells, constituting 95% of the epidermis,[10] while Merkel cells, melanocytes and Langerhans cells are also present. The epidermis can be further subdivided into the following strata or layers (beginning with the outermost layer):[11]

Keratinocytes in the stratum basale proliferate through mitosis and the daughter cells move up the strata changing shape and composition as they undergo multiple stages of cell differentiation to eventually become anucleated. During that process, keratinocytes will become highly organized, forming cellular junctions (desmosomes) between each other and secreting keratin proteins and lipids which contribute to the formation of an extracellular matrix and provide mechanical strength to the skin.[12]Keratinocytes from the stratum corneum are eventually shed from the surface (desquamation).

The epidermis contains no blood vessels, and cells in the deepest layers are nourished by diffusion from blood capillaries extending to the upper layers of the dermis.

The epidermis and dermis are separated by a thin sheet of fibers called the basement membrane, and is made through the action of both tissues. The basement membrane controls the traffic of the cells and molecules between the dermis and epidermis but also serves, through the binding of a variety of cytokines and growth factors, as a reservoir for their controlled release during physiological remodeling or repair processes.[13]

The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis provides tensile strength and elasticity to the skin through an extracellular matrix composed of collagen fibrils, microfibrils, and elastic fibers, embedded in hyaluronan and proteoglycans.[12] Skin proteoglycans are varied and have very specific locations.[14] For example, hyaluronan, versican and decorin are present throughout the dermis and epidermis extracellular matrix, whereas biglycan and perlecan are only found in the epidermis.

It harbors many mechanoreceptors (nerve endings) that provide the sense of touch and heat. It also contains the hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic vessels and blood vessels. The blood vessels in the dermis provide nourishment and waste removal from its own cells as well as for the epidermis.

The dermis is tightly connected to the epidermis through a basement membrane and is structurally divided into two areas: a superficial area adjacent to the epidermis, called the papillary region, and a deep thicker area known as the reticular region.

The papillary region is composed of loose areolar connective tissue.This is named for its fingerlike projections called papillae that extend toward the epidermis. The papillae provide the dermis with a "bumpy" surface that interdigitates with the epidermis, strengthening the connection between the two layers of skin.

The reticular region lies deep in the papillary region and is usually much thicker. It is composed of dense irregular connective tissue, and receives its name from the dense concentration of collagenous, elastic, and reticular fibers that weave throughout it. These protein fibers give the dermis its properties of strength, extensibility, and elasticity. Also located within the reticular region are the roots of the hair, sebaceous glands, sweat glands, receptors, nails, and blood vessels.

The hypodermis is not part of the skin, and lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It consists of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes (the hypodermis contains 50% of body fat). Fat serves as padding and insulation for the body. Another name for the hypodermis is the subcutaneous tissue.

Microorganisms like Staphylococcus epidermidis colonize the skin surface. The density of skin flora depends on region of the skin. The disinfected skin surface gets recolonized from bacteria residing in the deeper areas of the hair follicle, gut and urogenital openings.

The epidermis of fish and of most amphibians consists entirely of live cells, with only minimal quantities of keratin in the cells of the superficial layer. It is generally permeable, and in the case of many amphibians, may actually be a major respiratory organ. The dermis of bony fish typically contains relatively little of the connective tissue found in tetrapods. Instead, in most species, it is largely replaced by solid, protective bony scales. Apart from some particularly large dermal bones that form parts of the skull, these scales are lost in tetrapods, although many reptiles do have scales of a different kind, as do pangolins. Cartilaginous fish have numerous tooth-like denticles embedded in their skin, in place of true scales.

Sweat glands and sebaceous glands are both unique to mammals, but other types of skin gland are found in other vertebrates. Fish typically have a numerous individual mucus-secreting skin cells that aid in insulation and protection, but may also have poison glands, photophores, or cells that produce a more watery, serous fluid. In amphibians, the mucus cells are gathered together to form sac-like glands. Most living amphibians also possess granular glands in the skin, that secrete irritating or toxic compounds.[15]

Although melanin is found in the skin of many species, in the reptiles, the amphibians, and fish, the epidermis is often relatively colourless. Instead, the colour of the skin is largely due to chromatophores in the dermis, which, in addition to melanin, may contain guanine or carotenoid pigments. Many species, such as chameleons and flounders may be able to change the colour of their skin by adjusting the relative size of their chromatophores.[15]

The epidermis of birds and reptiles is closer to that of mammals, with a layer of dead keratin-filled cells at the surface, to help reduce water loss. A similar pattern is also seen in some of the more terrestrial amphibians such as toads. However, in all of these animals there is no clear differentiation of the epidermis into distinct layers, as occurs in humans, with the change in cell type being relatively gradual. The mammalian epidermis always possesses at least a stratum germinativum and stratum corneum, but the other intermediate layers found in humans are not always distinguishable. Hair is a distinctive feature of mammalian skin, while feathers are (at least among living species) similarly unique to birds.[15]

Birds and reptiles have relatively few skin glands, although there may be a few structures for specific purposes, such as pheromone-secreting cells in some reptiles, or the uropygial gland of most birds.[15]

Skin performs the following functions:

Skin is a soft tissue and exhibits key mechanical behaviors of these tissues. The most pronounced feature is the J-curve stress strain response, in which a region of large strain and minimal stress exists, and corresponds to the microstructural straightening and reorientation of collagen fibrils.[18] In some cases the intact skin is prestreched, like wetsuits around the diver's body, and in other cases the intact skin is under compression. Small circular holes punched on the skin may widen or close into ellipses, or shrink and remain circular, depending on preexisting stresses.[19]

The term "skin" may also refer to the covering of a small animal, such as a sheep, goat (goatskin), pig, snake (snakeskin) etc. or the young of a large animal.

The term hides or rawhide refers to the covering of a large adult animal such as a cow, buffalo, horse etc.

Skins and hides from the different animals are used for clothing, bags and other consumer products, usually in the form of leather, but also as furs.

Skin from sheep, goat and cattle was used to make parchment for manuscripts.

Skin can also be cooked to make pork rind or crackling.

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Skin - Wikipedia, the free encyclopedia

Cells in animals and in plants that are capable of becoming any other type of cell in that organism and then reproducing more of those cells. Despite the fact that stem cell research is in its infancy, many cosmetics companies claim they are successfully using plant-based or human-derived stem cells in their anti-aging products. The claims run the gamut, from reducing wrinkles to repairing elastin to regenerating cells, so the temptation for consumers to try these products is intense.

The truth is that stem cells in skincare products do not work as claimed; they simply cannot deliver the promised results. In fact, they likely have no effect at all because stem cells must be alive to function as stem cells, and by the time these delicate cells are added to skincare products, they are long since dead and, therefore, useless. Actually, its a good thing that stem cells in skincare products cant work as claimed, given that studies have revealed that they pose a potential risk of cancer.

Plant stem cells, such as those derived from apples, melons, and rice, cannot stimulate stem cells in human skin; however, because they are derived from plants they likely have antioxidant properties. Thats good, but its not worth the extra cost that often accompanies products that contain plant stem cells. Its also a plus that plant stem cells cant work as stem cells in skincare products; after all, you dont want your skin to absorb cells that can grow into apples or watermelons!

There are also claims that because a plants stem cells allow a plant to repair itself or to survive in harsh climates, these benefits can be passed on to human skin. How a plant functions in nature is completely unrelated to how human skin functions, and these claims are completely without substantiation. It doesnt matter how well the plant survives in the desert, no matter how you slather such products on your skin, you still wont survive long without ample water, shade, clothing, and other skin-protective elements.

Another twist on the stem cell issue is that cosmetics companies are claiming they have taken components (such as peptides) out of the plant stem cells and made them stable so they will work as stem cells would or that they will influence the adult stem cells naturally present in skin. In terms of these modified ingredients working like stem cells, this theory doesnt make any sense because stem cells must be complete and intact to function normally. Using peptides or other ingredients to influence adult stem cells in skin is something thats being explored, but to date scientists are still trying to determine how that would work and how it could be done safely. For now, companies claiming theyve isolated substances or extracts from stem cells and made them stable are most likely not telling the whole story. Currently, theres no published, peer-reviewed research showing these stem cell extracts can affect stem cells in human skin.

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stem cells - Cosmetic Ingredient Dictionary: Cosmetics Cop ...

Neurons created from chemically induced neural stem cells. The cells were created from skin cells that were reprogrammed into neural stem cells using a cocktail of only nine chemicals. This is the first time cellular reprogramming has been accomplished without adding external genes to the cells. (credit: Mingliang Zhang, PhD, Gladstone Institutes)

Scientists at the Gladstone Institutes have used chemicals to transform skin cells into heart cells and brain cells, instead of adding external genes making this accomplishment a breakthrough, according to the scientists.

The research lays the groundwork for one day being able to regenerate lost or damaged cells directly with pharmaceutical drugs a more efficient and reliable method to reprogram cells and one that avoids medical concerns surrounding genetic engineering.

Instead, in two studies published in an open-access paper in Scienceand in Cell Stem Cell, the team of scientists at the Roddenberry Center for Stem Cell Biology and Medicine at Gladstone used chemical cocktails to gradually coax skin cells to change into organ-specific stem-cell-like cells and ultimately into heart or brain cells.

This method brings us closer to being able to generate new cells at the site of injury in patients, said Gladstone senior investigatorSheng Ding, PhD, the senior author on both studies. Our hope is to one day treat diseases like heart failure or Parkinsons disease with drugs that help the heart and brain regenerate damaged areas from their own existing tissue cells. This process is much closer to the natural regeneration that happens in animals like newts and salamanders, which has long fascinated us.

Chemically Repaired Hearts

A human heart cell that was chemically reprogrammed from a human skin cell (credit: Nan Cao/Gladstone Institutes)

Transplanted adult heart cells do not survive or integrate properly into the heart and few stem cells can be coaxed into becoming heart cells.

Instead, in theSciencestudy, the researchers used a cocktail of nine chemicals to change human skin cells into beating heart cells. By trial and error, they found the best combination of chemicals to begin the process by changing the cells into a state resembling multipotent stem cells (cells that can turn into many different types of cells in a particular organ). A second cocktail of chemicals and growth factors then helped transition the cells to become heart muscle cells.

With this method, more than 97% of the cells began beating, a characteristic of fully developed, healthy heart cells. The cells also responded appropriately to hormones, and molecularly, they resembled heart muscle cells, not skin cells. Whats more, when the cells were transplanted into a mouse heart early in the process, they developed into healthy-looking heart muscle cells within the organ.

The ultimate goal in treating heart failure is a robust, reliable way for the heart to create new muscle cells, said Srivastava, co-senior author on the Science paper. Reprogramming a patients own cells could provide the safest and most efficient way to regenerate dying or diseased heart muscle.

Rejuvenating the brain withneural stem cell-like cells

In the second study, authored by Gladstone postdoctoral scholar Mingliang Zhang, PhD, and published inCell Stem Cell, the scientists created neural stem-cell-like cells from mouse skin cells using a similar approach.

The chemical cocktail again consisted of nine molecules, some of which overlapped with those used in the first study. Over ten days, the cocktail changed the identity of the cells, until all of the skin-cell genes were turned off and the genes of the neural stem-cell-like cells were gradually turned on.

When transplanted into mice, theneural stem-cell-like cells spontaneously developed into the three basic types of brain cells: neurons, oligodendrocytes, and astrocytes. The neuralstem-cell-like cells were also able to self-replicate, making them ideal for treating neurodegenerative diseases or brain injury.

With their improved safety, these neural stem-cell-like cells could one day be used for cell replacement therapy in neurodegenerative diseases like Parkinsons disease and Alzheimers disease, according to co-senior authorYadong Huang, MD, PhD, a senior investigator at Gladstone. In the future, we could even imagine treating patients with a drug cocktail that acts on the brain or spinal cord, rejuvenating cells in the brain in real time.

Gladstone Institutes | Chemically Reprogrammed Beating Heart Cell

Abstract ofConversion of human fibroblasts into functional cardiomyocytes by small molecules

Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells to specific homogeneous, functional cell types is challenging. Here we show that cardiomyocyte-like cells can be generated by treating human fibroblasts with a combination of nine compounds (9C). The chemically induced cardiomyocyte-like cells (ciCMs) uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. 9C treatment of human fibroblasts resulted in a more open-chromatin conformation at key heart developmental genes, enabling their promoters/enhancers to bind effectors of major cardiogenic signals. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to ciCMs. This pharmacological approach for lineage-specific reprogramming may have many important therapeutic implications after further optimization to generate mature cardiac cells.

Abstract ofPharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation

Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes.

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Scientists Turn Skin Cells Into Heart and Brain Cells ...

Submitted by Lifeline Skin Care on Wed, 2013-05-15 00:00

Biologists are working diligently to find ways to repair diseased tissues or spinal cord injuries with stem cells. Scientists dont have all of those answers yet, but heres what they have figured out: how to repair skin aging with stem cells. Front and center of all of that attention is Lifeline Skin Carethe first anti-aging skin care brand based on human, non-embryonic stem cells.

Human stem cells have the remarkable ability to develop into many different cell types in the bodylungs, liver, hair, skin, etc. But as we get older, the role of stem cells changesand stem cells become the chief repair mechanism for tissue that has become aged, injured or damaged. Adult stem cells remain dormant until they detect cellular damage; then they work to repair or replace the damaged cell. Its this ability that makes stem cells of great interest in repairing skin aging.

The nutrient-rich growth factors, peptides and proteins that are contained in the stem cells are the workhorses for skin repair. The growth factors are responsible for cellular growth, proliferation and repair. They play an important role in maintaining healthy skin structure and function. They help repair wounds; they help promote the formation of collagen; they help regenerate new, healthy tissue. The result: reduced hyperpigmentation, enhanced elasticity, and reduced fine lines and wrinkles.

The genes that are most important to the health and appearance of the skin are Elastin, Collagen, Epidermal Growth Factors, Keratinocyte Growth Factors and Fibroblast Growth Factors.

Laboratory studies showed how exposure to Lifeline creams can increase the expression level of key proteins:

Collagen is the most important protein and provides structure and firmness to the skin. Lifelines stem cell extract increased collagen 42%-55%.

Elastin is responsible for load-bearing and elasticity. Its crucial for keeping skin smooth, supple, firm and tight. The key ingredient in Lifelines stem cell extract increased elastin 46%.

Epidermal growth factors (EGF) stimulate cells to divide. Its natural for skin cells to continue to divide, but with age this process slows. Epidermal growth factors help speed up the renewal process, speeding the production of new, healthy skin cells. The stem cell growth factors contained in Lifelines stem cell extract increased EGF a remarkable 436%.

Keratinocyte growth factors (KGF) help repair injured skin by stimulating cellular proliferation.The stem cell growth factors contained in Lifelines stem cell extract increased KGF 58%.

Fibroblast growth factors (FGF) help repair damaged tissue and promote wound healing. They also play an important role in repairing post-procedural skin damage. The growth factors contained in Lifelines stem cell extract increased FGF 200%.

Lifeline Skin Care serums contain human stem cell growth factors which are taken from human, non-embryonic stem cells. It is this mixture that regulates collagen, elastin and cell proliferation, making the skin cells healthier, stronger and younger-looking.

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The Benefits of Using Growth Factors from Human Stem Cells ...

As human stem cells and their role in skin physiology, wound repair, aging, and rejuvenation is the subject of our own work, we have a lot to say on the subject. As our goal here is education at a consumer level, we struggle mightily to express complex concepts and research results in terms that can be appreciated by all, including non-scientists. But sometimes fine shades of meaning have big consequences, and we dont want to compromise on the bare faced truth mission either. It is frankly a challenge, and Im sure we fail for the most part. So we apologize in advance and ask you to bear with us. Hopefully we will get better at this as time goes on.

In a prior post we introduced the subject of mesenchymal stem cells. Next we will take you a bit further down the path of understanding what these particular stem cells have to do with skin and aging. I thought I would put this in outline form. See if this makes it any easier to digest. Here goes.

Not all stem cells are the same. There are many varieties.

Mesenchymal stem cells (MSCs) are one type; they form a key part of the human bodys defense against injury and stress.

MSCs can be found in many places in the body bone marrow, fat, tooth roots, around blood vessels, etc. Each of these are called niches and reflect the home environment of that type of MSC. There is increasing evidence that marked differences exist in the biology of MSCs that are dependent on the tissue of origin. Indeed this niche factor appears to be the main source of variation in the biological properties of MSCs (De Bari et al., 2008; Augello, Kurth & De Bari, 2010).

Thus, not all MSCs are the same.

MSCs migrate to damaged areas of the body. There they act as first responders. Their primary role is command and control telling local tissue what to do, and organizing cells of the immune system which are the worker bees.

All communication among MSCs and between MSCs and other cells (e.g. damaged skin cells) uses biochemicals called cytokines.

There are hundreds of cytokines, each with a specific message (e.g. hey fibroblasts, lets make some more collagen). Multiple messages are in play at any time in an MSC mediated response. The messages are tightly coordinated so they reach the right cells at the right time for the proper work to be done. Some are very short distance and some are medium or long distance.

Cytokines can be classified into families. Some are growth factors (make more cells), some are chemokines (bring me some phagocytic cells), and many are involved in protein synthesis inside cells they target.

MSC cells themselves can differentiate into needed cells for rebuilding damaged tissue. But it turn out that that is a minor part of what they do, not the major thing. In skin in particular, MSCs as bricks in rebuilding is unlikely except in severe damage (e.g. burns).

Aging skin reflects both intrinsic cell and tissue level changes (senescence) and a process of continual damage (e.g. from sun, chemicals, disease) and repair (via several mechanisms, including calling 911 to bring MSCs to the area).

There are unique MSC-like cells that live in very small numbers in the bottom of hair follicles. This is their niche (remember, not all MSCs are the same). There are also perivascular (around blood vessel) MSCs in the dermis of skin (deeper).

These local stem cells have particular roles to play in maintenance of growth, and replacing senescent cells (all cells die of old age eventually). But in terms of damage, other MSCs migrate to the area from guess where? The bone marrow. Seems like that is the special role of that particular MSC niche.

That scenario will be no surprise to those who know that the bone marrow is also where all the blood cells (red corpuscles and white immune system cells) are made and exported via the blood stream to perform functions throughout the body. In fact, bone marrow MSCs and bone marrow hematopoetic stem cells live in very close proximity in the bone marrow. These are the same cells that get replaced when a bone marrow transplant is performed.

When skin undergoes repair, all these mechanisms must act together in a coordinated fashion. Again, that control seems to be the specialty of marrow-derived MSCs secreting very specific patterns of cytokines. Those cytokine patterns are what determines that the right thing happens at the right time. E.g. you dont want to build new cells until you have mopped up the debris from damaged tissue. That would be like painting over old peeling wallpaper. Ask your local contractor. Demolition happens first, then rebuilding.

When you hear about products that contain stem cells, you should ask several questions. First, you should read Dr. Georges post about plant stem cells (dont work), creams that have nothing to do with stem cells whatsoever except using it as a deceitful marketing term (e.g. Biologics Stem Cell Cream). You can filter these out right away.

That leaves you with human stem cells. Now, you will not find cosmeceutical products on the market that contain human stem cells. That would be considered a biologic by FDA standards, and would be regulated like a drug or device. The reason is that whole cells contain (other peoples) DNA, and may also carry disease.

While human stem cells themselves wont be in any products, they can be grown in culture (in vitro, or outside the body) in a laboratory. When they do so, if they are well fed and happy, they tend to divide to make new daughter cells. When they are doing so, they communicate with one another via cytokines. Remember the messenger molecules we spoke of above? This is the basic language of stem cells. Again, if the conditions are right, they chatter away as they expand in culture (more of them, coming closer together). As they start to crowd up against each other (we call that confluence) the message changes. More of those short distance cytokines are produced. Some are transferred from one cell to next one touching it (we call that a paracrine message). The MSCs start to slow down their proliferation when the numbers reach confluence. At this point the cell biologist may transfer some of those cells to new flasks, where they will be less crowded, and will resume proliferation. This is a called a passage.

Now, if you remove some of the nutrient rich fluid that bathes the MSCs in culture, you will find that it contains a lot of cytokines. This is called conditioned medium. It is cell growth medium conditioned by the many cytokines secreted by the MSCs. Its like capturing a whole bunch of cell-to-cell conversations all at once. An analogy might be your cellular telephony system. If you could grab 5 second sample of all the conversations going through one cell tower, it would indeed be a tower of babble But your cell system is clever enough to sort all those words into the right pathway to make a conversation.

So, here is the discovery that led to a whole new generation of anti-aging skin care products. If you take that conditioned media and put it on skin, you can observe immediate improvements in skin texture, tone and color. If you keep applying it, you will see structural changes (increase collagen production) with diminution of wrinkles. It has interesting side effects. Minor cuts and abrasions heal very quickly. Angry red areas seem to disappear.

That defines the first generation products whose key active ingredients are made by stem cells in vitro. But that is only the start. We now are gaining insight into the stem cytokines themselves, and the patterns they form. We know that they talk about a lot more than growth, and if can discern what they are saying and how they say it (in other words decipher their language) we can change the cytokine composition of the conditioned medium. We can them communicate back with the MSCs in culture in their language. In doing so (I will leave out a lot of proprietary steps here) we can get them to change their message by responding to ours. We can optimize it for different situations. So, it is no longer one product (a bunch of cytokines) but a very clever set of stem cells making products for whatever condition we require.

This is a lot for one post. Im up to about 1,500 words. I will leave it here for now, and let interested folks who have read this far digest and ask any questions you may have.

One last thing this is very exciting stuff, and has many impacts beyond skin & aging. This is not mere cosmetics this is core cellular physiology. And how grand it is (for a change) that skin science gets to be on the forefront of research rather than on the back burner.

Await your comments.

Dr. John

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Stem Cells and Skin Part 3: It's the Cytokines ...

Introduction

The announcement of the ability to produce embryonic cell-like lines from ordinary skin cells has the news media scrambling to get feedback about the possible efficacy of such lines in stem cell therapies. Many politicians have landed on one side or the other, with liberals saying that embryonic stem cell research is still necessary1 and conservatives claiming that all embryonic research should be halted. The marketplace of science will eventually weigh-in on which method(s) are used in real therapies.

Embryonic stem cell (ESC) research has been a hot topic, with conservatives saying that such research is morally unacceptable and liberals saying that conservatives value a clump of cells more than people who have serious disabling diseases. Several groups of medical researchers (including James Thomson, the first person to culture ESC) recently showed that normal skin cells can be reprogrammed to an embryonic state, producing what are now called induced pluripotent stem (iPS) cells. Originally performed in mice in June, 2007,2 researchers took four genes OCT3/4, SOX2, KLF4, and c-MYC and incorporated those genes into the nucleus of cells to induce pluripotency. Such lines could be expanded indefinitely and could differentiate to form numerous kinds of different tissues.

Just five months after the mouse study was published, the feat was repeated by three separate laboratories using human skin cells.3 One research group used the same genes as those used in the mouse study, whereas a second group used OCT3, SOX2, NANOG and LIN28. The techniques were efficient enough to generate one cell line for every 5-10 thousand cells treated. Although not extremely efficient, it is quite usable, since it is possible to obtain hundreds of thousands to millions of cells to carry out these kinds of studies. The technique was recently replicated for adult human skin cells,4 instead of skin cell lines, demonstrating that it could be used to generate patient-specific cell lines.

Studies using iPS cell lines have shown that those cells undergo similar changes compared to what is observed with embryonic stem cells. Cell populations grew at the same rate, telomerase (which preserves the ends of chromosomes) was present in both iPS and ESC. Severalgenes that are silenced in fibroblasts, but active in ESC, were also active in the iPS cells. The iPS cell lines could be differentiated into heart muscle and neuronal cells, in addition to basic cell types (ectoderm, mesoderm, and endoderm). Gene expression assays showed that 5,000 genes from iPS cells showed a five-fold difference in expression compared to those in fibroblasts, although 1,267 genes had a five-fold difference in expression between ESC and iPS cells. According to the James Thomson study, "The human iPS cells described here meet the defining criteria we originally proposed for human ES cells (14), with the significant exception that the iPS cells are not derived from embryos."3

Originally, the new technique is not without its own set of problems, although within two years, virtually all had been resolved. One of the original genes used for reprogramming (c-MYC) has been shown to produce tumors and cancers. Obviously, it would not be a good choice for patient therapy. However, this gene was eliminated in some of the later techniques.5 The second problem was that the genes were originally introduced through the use of a retrovirus that incorporates into the host cell DNA. Depending upon where the gene sequence inserts, it may cause trouble (including mutations and cancers). Those who watched the I am Legend movie will remember that a retrovirus-derived cancer treatment was responsible for turning the surviving members of the human race into an army of grotesque monsters. Although such a transformation is not possible, the initiation of cancer in even a small number of treated patients would make such treatments unusable for human therapy. Two years later the problem of using a retroviral system for reprogramming was solved by switching to a simple lentivirus reprogramming system.6 Within weeks, other researchers went a step further, eliminating viral reprogramming altogether by using reprogramming genes (OCT4, SOX2, NANOG, LIN28, c-Myc, and KLF4) cloned into a circular piece of DNA called a plasmid.7 Subsequent culture of of the iPS over a period of weeks resulted in the complete loss of the plasmid, but with continued pluripotency. The potential of iPS cells is so great that the researcher who first grew ESC in culture is now one of the leading proponents of iPS stem cell research.

A more recent, but somewhat uncertain potential problem has been identified more recently. Since iPS cells are derived from adult tissues, they tend to harbor some of the same epigenetic profiles as those adult tissues from which they are derived. As cells age or differentiate, certain genes are turned on or off through methylation of those gene's promoters. The process prevents those cells from undergoing additional changes that might cause the cells to lose their differentiated properties. When adults cells are induced to pluripotency, some of those epigenetic profiles are retained in the iPS cells.8 How will these vestiges of adult cells affect iPS ability to differentiate into cells that are useful for disease models or therapy? At this point, we don't know for sure. However, my guess is that different ESC lines will exhibit different epigenetic profiles, as will specific isolates of iPS cells. Although researchers have found no problems in producing differentiated iPS lines, some of these epigenetic changes might interfere with the ultimate function of these cells as differentiated cell lines.

Even with these issues, research institutes are beginning to focus their stem cell research on iPS cells. Cedars-Sinai Medical Center recently opened its Induced Pluripotent Stem Cell Core Production Facility in late 2011, according to their press release.9

Induction of pluripotency to produce embryonic-like stem cells is the hot topic in stem cell research. The fact that human iPS cells have been produced in many different laboratories after the initial animal studies shows that the technique is robust and easily reproducible. In contrast, the competing technique, human somatic cell nuclear transfer (cloning), has never been transferred from animal studies to human application, despite years of attempts. At this point, it seems pretty certain that the iPS technique will soon replace ESC as the preferred means of generating human stem cell lines. However, the disadvantage of iPS cells is that the cell lines produced would be patient specific (only useful for the intended patient), whereas the establishment of ESC lines allows biotech companies to patent the lines in order to make lots of money.

http://www.godandscience.org/doctrine/reprogrammed_stem_cells.html Last Modified October 6, 2011

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Induced Pluripotent Stem Cells (iPS) from Human Skin ...

knowledge center home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

A video on how stem cells work and develop.

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells.

The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of healthy adults. They were then implanted onto the surface of the brains of the mice.

Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones.

The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases.

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to our weekly or daily newsletters to ensure that you stay up-to-date with the latest news.

This stem cells information section was written by Peter Crosta for Medical News Today in September 2008 and was last updated on 19 July 2013. The contents may not be re-produced in any way without the permission of Medical News Today.

Disclaimer: This informational section on Medical News Today is regularly reviewed and updated, and provided for general information purposes only. The materials contained within this guide do not constitute medical or pharmaceutical advice, which should be sought from qualified medical and pharmaceutical advisers.

Please note that although you may feel free to cite and quote this article, it may not be re-produced in full without the permission of Medical News Today. For further details, please view our full terms of use

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What are Stem Cells? Medical News Today

April 28, 2016

A pair of molecular signals controls skin and hair color in mice and humansand could be targeted by new drugs to treat skin pigment disorders like vitiligo, according to a report by scientists at NYU Langone Medical Center.

Finding ways to activate these pathways, researchers say, could lead to therapies that repigment skin cells damaged in vitiligo, a disfiguring illness marked by the loss of skin pigmentation, leaving a blotchy, white appearance. The same pathways could serve as targets for drug therapies that repigment grayed hair cells for people seeking a younger look but who are allergic to cosmetic dyes. Such therapies might even one day reinforce pigment to correct discoloration around scars.

In experiments in mice and human cells, researchers found that control of these skin and early-stage hair cells, known as melanocyte stem cells, is regulated by cell-to-cell signaling reactions. These reactions are part of the endothelin receptor type B (EdnrB) and the Wnt signaling pathways.

Previous research had shown that endothelin proteins and the EdnrB pathway help control blood vessel development, as well as some aspects of cell growth and division, the scientists say. But they believe that their new findings, to be published in the journal Cell Reports online April 28, are the first evidence tying the signaling pathways to the routine growth of cells that produce pigment (melanocytes) and provide color to skin and hair.

They say the study is the first to outline the link between EdnrB and Wnt signaling, confirming that EdnrB coordinates the rapid reproduction of melanocyte stem cells.

"Our study results show that EdnrB signaling plays a critical role in growth and regeneration of certain pigmented skin and hair cells and that this pathway is dependent on a functioning Wnt pathway," says study senior investigator and cell biologist Mayumi Ito, PhD. Ito is an associate professor in the Ronald O. Perelman Department of Dermatology at NYU Langone and a member of NYU Langone's Helen L. and Martin S. Kimmel Center for Stem Cell Biology.

Among the study's key findings, Ito reports, was that mice bred to be deficient in the EdnrB pathway experienced premature graying of their fur.

Study co-lead investigator and postdoctoral fellow Wendy Lee, PhD, says the pathway's involvement in determination of hair color was "clearly evident" in the mice when she first examined them.

In further experiments in mice, stimulating the EdnrB pathway resulted in a 15-fold increase in melanocyte stem cell pigment production within two months, producing what Ito calls "hyperpigmentation." Wounded skin in normally white mice became dark upon healing.

In the latest study, Ito and her team found that blocking Wnt signaling stalled stem cell growth and the maturing of stem cells into normally functioning melanocytes, even when endothelin proteins were present. This led to mice with unpigmented grayish coats.

Ito says her team plans further investigations into how other cell repair and signaling pathways interact with EdnrB and melanocyte stem cells.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, vitiligo occurs in about 1 percent of people worldwide.

Explore further: New research provides clues on why hair turns gray

A new study by researchers at NYU Langone Medical Center has shown that, for the first time, Wnt signaling, already known to control many biological processes, between hair follicles and melanocyte stem cells can dictate ...

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Stem cell study finds mechanism that controls skin and ...

Scientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. It is believed that stem cell therapies hold the promise of replacing cells damaged through injury or illness. Diseases or conditions that might be treated through stem cell therapy include Parkinson's disease, multiple sclerosis, cardiac disease and spinal cord injuries.

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. This latest research will be published in the journal Cell online May 15 and in print June 6.

The technique used by Drs. Mitalipov, Paula Amato, M.D., and their colleagues in OHSU's Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, is a variation of a commonly used method called somatic cell nuclear transfer, or SCNT. It involves transplanting the nucleus of one cell, containing an individual's DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.

"A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells. Furthermore, because these reprogrammed cells can be generated with nuclear genetic material from a patient, there is no concern of transplant rejection," explained Dr. Mitalipov. "While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine."

Another noteworthy aspect of this research is that it does not involve the use of fertilized embryos, a topic that has been the source of a significant ethical debate.

The Mitalipov team's success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs showed that human egg cells appear to be more fragile than eggs from other species. Therefore, known reprogramming methods stalled before stem cells were produced.

To solve this problem, the OHSU group studied various alternative approaches first developed in monkey cells and then applied to human cells. Through moving findings between monkey cells and human cells, the researchers were able to develop a successful method.

The key to this success was finding a way to prompt egg cells to stay in a state called "metaphase" during the nuclear transfer process. Metaphase is a stage in the cell's natural division process (meiosis) when genetic material aligns in the middle of the cell before the cell divides. The research team found that chemically maintaining metaphase throughout the transfer process prevented the process from stalling and allowed the cells to develop and produce stem cells.

"This is a remarkable accomplishment by the Mitalipov lab that will fuel the development of stem cell therapies to combat several diseases and conditions for which there are currently no treatments or cures," said Dr. Dan Dorsa, Ph.D., OHSU Vice President for Research. "The achievement also highlights OHSU's deep reproductive expertise across our campuses. A key component to this success was the translation of basic science findings at the OHSU primate center paired with privately funded human cell studies."

One important distinction is that while the method might be considered a technique for cloning stem cells, commonly called therapeutic cloning, the same method would not likely be successful in producing human clones otherwise known as reproductive cloning. Several years of monkey studies that utilize somatic cell nuclear transfer have never successfully produced monkey clones. It is expected that this is also the case with humans. Furthermore, the comparative fragility of human cells as noted during this study, is a significant factor that would likely prevent the development of clones.

"Our research is directed toward generating stem cells for use in future treatments to combat disease," added Dr. Mitalipov. "While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning."

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Human skin cells converted into embryonic stem cells ...

Researchers at the Universit Libre de Bruxelles, ULB identify a new stem cell population in the skin epidermis responsible for tissue repair.

The skin, which is an essential barrier that protects our body against the external environment, undergoes constant turnover throughout life to replace dead cells that are constantly sloughed off from the skin surface. During adult life, the number of cells produced must exactly compensate the number of cells lost. Different theories have been proposed to explain how this delicate balance is achieved.

In a new study published in Nature, researchers lead by Pr. Cdric Blanpain, MD/PhD, FNRS/FRS researcher and WELBIO investigator at the IRIBHM, Universit libre de Bruxelles, Belgium, in collaboration with Pr. Benjamin Simons, University of Cambridge, UK, demonstrate the existence of a new population of stem cells that give rise to progenitor cells that ensure the daily maintenance of the epidermis and demonstrate the major contribution of epidermal stem cells during wound healing.

In this new study, Guilhem Mascr and colleagues used novel genetic lineage tracing experiments to fluorescently mark two distinct epidermal cell populations, and follow their survival and contribution to the maintenance of the epidermis overtime. Interestingly, in doing so, they uncover the existence of two types of dividing cells. One population of proliferative cells presented a very long term survival potential while the other population is progessively lost overtime. In collaboration with Pr. Benjamin D. Simons, the authors developed a mathematical model of their lineage tracing analysis. The authors proposed that the skin epidermis is hierarchically organized with slow cycling stem cells residing on the top of the cellular hierarchy that give rise to more rapidly cycling progenitor cells that ensure the daily maintenance of the skin epidermis. Analysis of cell proliferation confirms the existence of slow cycling stem cells and gene profiling experiments demonstrate that the stem and the progenitors cells are characterized by distinct gene expression.

Importantly, by assessing the contribution these two populations of cells during wound healing, they found that only stem cells are capable of extensive tissue regeneration and undergo major expansion during this repair process, while the progenitors did not expand significantly, and only provide a short-lived contribution to the wound healing response. As well as resolving the cellular hierarchy of epidermis, this is the first demonstration of a critical role of epidermal SC during wound healing. "It was amazing to see these long trails of cells coming from a single stem cell located at a very long distance from the wound to repair the epidermis" comments Cdric Blanpain, the senior author of this study.

In conclusion, this work demonstrates the existence of slow-cycling stem cells that promote tissue repair and more rapidly cycling progenitors that ensure the daily maintenance of the epidermis. A similar population of slow cycling stem cells that can be rapidly mobilized in case of sudden need has been observed in other tissues, such as the blood, muscle and hair follicle, and the partition between rapidly cycling progenitors and slow cycling stem cells could be relatively conserved across the different tissues. This study may have important implications in regenerative medicine in particular for skin repair in severely burnt patients or in chronic wounds.

This work was supported by the FNRS, the " Brain back to Brussels " program from the Brussels Region, the program d'excellence CIBLES of the Wallonia Region, a research grant from the Fondation Contre le Cancer, the ULB foundation, the fond Gaston Ithier. Cdric Blanpain is an investigator of WELBIO and is supported by a starting grant of the European Research Council (ERC) and the EMBO Young Investigator Program.

Story Source:

The above post is reprinted from materials provided by Libre de Bruxelles, Universit. Note: Materials may be edited for content and length.

See the article here:
Newly identified stem cell population in skin's epidermis ...

Ok. Bits of this film are a little grim, but its worth it. Well, go on then!

Amazing right? And yes, its real! I have to admit I double-checked the date when my friend forwarded me the National Geographic link, but April first it was not. Researchers at the University of Pittsburgs McGowan Institute for Regenerative Medicine have made the skin cell spray gun a very real, very effective treatment for burn victims.

So how does it work? At its core, this treatment relies on the unique properties of stem cells, so thats where Ill begin. Stem cells

Stem cells have fascinated biologists for years. They are unique amongst all other cells of the body in two ways; their capacity for self-renewal, and their ability to give rise to many different cell types.

Embryonic stem cells, which frequently (and controversially) make the news, are derived from a developing fetus. They are the ultimate in stem cell-iness because they have the potential to direct the development of an entire organism. This means that they contain all the information need to make muscles, nerves, eyes etc. And naturally this pluripotency (from the Latin pluri meaning many, and potency or potential) seemed like a fantastic quality for biologist to understand. Not only were there fundamental developmental principles to be learned, the medical applications were endless. However, glaring ethical issues arose regarding the taking of a life to save a life (that I wont get into here) that have resulted in the stringent regulation of embryonic stem cell research.

And so researchers turned to adult stem cells. While adult stem cells are not as versatile as embryonic stem cells, they do have the potential to direct the development of certain cell lineages. For example hematopoietic stem cells, which reside in your bone marrow, can divide asymmetrically into all the different cells of your blood. Similarly, all the different layers of your skin have ancestral skin stem cells.

Research into embryonic stem cells resulted in the identification of certain genes that were expressed in, and required by, stem cells. In 2006, a Japanese group generated the first induced pluripotent stem cells. Since then much work has gone into understanding the potential of these induced stem cells. However due to genetic manipulation and lack of correct genomic imprinting (small chemical modifications in our DNA that are laid down in the egg), induced pluripotent stem cells have the unfortunate ability to become cancerous. As detailed in a recent paper in Cell however, while these cells are not yet ready for the clinic, this should not prevent them from being used in a laboratory setting. Stem cells as a treatment

Bone marrow transplantation was the first example of a stem cell therapy. In 1959 the French surgeon Georges Math treated six nuclear power plant workers who had been so severely irradiated that their hematopoietic stem cell populations had been destroyed. The procedure has since been used with great success in the treatment of leukemia.

As with all transplants, the potential of the host rejecting the donor tissue exists. This rejection occurs because of subtle cellular differences between each and every one of us. Our immune system recognizes these differences as foreign, much as it would any other pathogenic invader, and mounts a formidable defense. With the development of tissue typing procedures and administration of immunosuppressive drugs, transplant rejection has significantly decreased.

By far the best way of avoiding rejection, however, is to transplant the recipients own tissue. In certain procedures, such as small areas of skin grafting, such auto-grafting is a viable option. But in others, such as in the case of organ transplantation, it is not. And this is where stem cells can sweep in and save the day.

Tissues in dishes

We have long had the capacity to grow cells in vitro (which literally means within a glass). Bacterial cells grow happily in test tubes when provided with simple nutrients and an incubator, as do yeast cells. Mammalian cells are a little more difficult to deal with, but again we have been culturing them in the lab for over a hundred years. All they require is a container to grow in that protects them from infection, liquid media containing essential amino acids and other nutrients, and a warm humid chamber in which to grow.

I am however talking about growing one type of cell at a time. Growing an organized tissue presents a far greater challenge. Not only do the cells have to grow and divide, they have to interact with one another and take on specialized roles within the tissue. Normally in our bodies external forces and small molecules send signals between cells that direct this process. Culturing a tissue in vitro requires a significant understanding of how the tissue forms, and an ability to isolate the stem cells from which the tissue is derived.

In the case of transplantation, the stem cells can be derived from the patient who will receive the cultured tissue, thus removing the chance of complications arising due to donor incompatibility. As you saw in the video, skin grafts have been performed in this way for quite some time, but with variable success.

The skin gun

And this is of course where the genius of the skin gun, and its inventor Joerg C. Gerlach, comes in; it bypasses the need for the in vitro tissue culturing. Skin stem cells that had been destroyed in the burn are replaced, and then the tissue is allowed to heal. As in the case of tissue culture in a lab, these cells require a sterile and nutrient rich environment to thrive. After the initial spraying, the wound is covered with a dressing that contains a synthetic circulatory system that brings nutrients to the infant skin and removes any toxins and waste products.

The speed and effectiveness of this treatment is out of this world. The guy in the video didnt even have a scar after his treatment. Perhaps the spray gun as a means of stem cell delivery is unique to skin regeneration, but there are a couple of features that should be transferable to other transplants, particularly the ability to enrich a patients own stem cells and re-apply them to damaged tissue. This will likely be advanced from burgeoning knowledge on where adult stem cells reside in our body, in so-called stem cell niches. With skin stem cell therapy now a reality, what will be next? Will we be able to re-grow more complex organs such as kidneys? Or will we be able to harvest healthy stem cells from a niche before a disease such as leukemia becomes debilitating? What do you think?

Bock, C., Kiskinis, E., Verstappen, G., Gu, H., Boulting, G., Smith, Z., Ziller, M., Croft, G., Amoroso, M., & Oakley, D. (2011). Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines Cell, 144 (3), 439-452 DOI: 10.1016/j.cell.2010.12.032

Hi Peter,

Thanks for the links. I should probably have pointed out in my article that this idea is not totally novel. The Australian plastic surgeon Dr. Fiona Wood has been using a similar technique for close to a decade. She has since started a company, http://www.avitamedical.com/index.php?ob=1&id=37. The technique was used extensively to treat burn victims of the Bali bombings in 2002. The recent development of the stem cell gun has basically increased the efficiency of the system, reduced damage caused to the stem cells during spraying, and made the technique more user friendly in a hospital setting.

However, I searched and searched and there is no Nature paper, which honestly baffled me too.

I was happy to see in that link that a clinical trial is in the works. Hopefully from that some concrete data can be collected as to the precise efficacy of the cell spray system, as well as a peer-reviewed article on the subject. It seems to me that burn experts are divided on the merit or value of the treatment. In my opinion the only way a consensus can be reached is through a thorough, scientific and transparent trial. But should the therapy prove itself in that setting, I think it is a fantastic advancement in the therapeutic use of adult stem cells.

Would this work on a aged skin, skin damaged other than fire, frostbite, gangrene, cancer, etc?

What about those sunbathers with leathery type of skin?

Thanks

Ha I like your idea about the leathery sun-worshipers! I think stem cell therapy like this has potential for aiding wound healing, ie where large amounts of skin have had to be removed. But I do not think it could help adult skin thats already present. Youd have to remove the whole leathery mess and start againa new era of cosmetic surgery?

See the rest here:
Spray on some stem cells and grow your own skin! | Katie PhD

What are Stem Cells?

Types of Stem Cells

Why are Stem Cells Important?

Can doctors use stem cells to treat patients?

Pros and Cons of Using Stem Cells

What are Stem Cells?

There are several different types of stem cells produced and maintained in our system throughout life. Depending on the circumstances and life cycle stages, these cells have different properties and functions. There are even stem cells that have been created in the laboratory that can help us learn more about how stem cells differentiate and function. A few key things to remember about stem cells before we venture into more detail:

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut.

Source ISSCR

Stem Cell History

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell is now known as induced pluripotent stem cells (iPSCs).

Source NIH

Types of Stem Cells

Adult Stem Cells (ASCs):

ASCs are undifferentiated cells found living within specific differentiated tissues in our bodies that can renew themselves or generate new cells that can replenish dead or damaged tissue. You may also see the term somatic stem cell used to refer to adult stem cells. The term somatic refers to non-reproductive cells in the body (eggs or sperm). ASCs are typically scarce in native tissues which have rendered them difficult to study and extract for research purposes.

Resident in most tissues of the human body, discrete populations of ASCs generate cells to replace those that are lost through normal repair, disease, or injury. ASCs are found throughout ones lifetime in tissues such as the umbilical cord, placenta, bone marrow, muscle, brain, fat tissue, skin, gut, etc. The first ASCs were extracted and used for blood production in 1948. This procedure was expanded in 1968 when the first adult bone marrow cells were used in clinical therapies for blood disease.

Studies proving the specificity of developing ASCs are controversial; some showing that ASCs can only generate the cell types of their resident tissue whereas others have shown that ASCs may be able to generate other tissue types than those they reside in. More studies are necessary to confirm the dispute.

Types of Adult Stem Cells

Embryonic Stem Cells (ESCs):

During days 3-5 following fertilization and prior to implantation, the embryo (at this stage, called a blastocyst), contains an inner cell mass that is capable of generating all the specialized tissues that make up the human body. ESCs are derived from the inner cell mass of an embryo that has been fertilized in vitro and donated for research purposes following informed consent. ESCs are not derived from eggs fertilized in a womans body.

These pluripotent stem cells have the potential to become almost any cell type and are only found during the first stages of development. Scientists hope to understand how these cells differentiate during development. As we begin to understand these developmental processes we may be able to apply them to stem cells grown in vitro and potentially regrow cells such as nerve, skin, intestine, liver, etc for transplantation.

Induced Pluripotent Stem Cells (iPSCs)

Induced pluripotent stem cells are stem cells that are created in the laboratory, a happy medium between adult stem cells and embryonic stem cells. iPSCs are created through the introduction of embryonic genes into a somatic cell (a skin cell for example) that cause it to revert back to a stem cell like state. These cells, like ESCs are considered pluripotent Discovered in 2007, this method of genetic reprogramming to create embryonic like cells, is novel and needs many more years of research before use in clinical therapies.

NIH

Why are Stem Cells Important?

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

Source NIH

Can doctors use stem cells to treat patients?

Some stem cells, such as the adult bone marrow or peripheral blood stem cells, have been used in clinical therapies for over 40 years. Other therapies utilizing stem cells include skin replacement from adult stem cells harvested from hair follicles that have been grown in culture to produce skin grafts. Other clinical trials for neuronal damage/disease have also been conducted using neural stem cells. There were side effects accompanying these studies and further investigation is warranted. Although there is much research to be conducted in the future, these studies give us hope for the future of therapeutics with stem cell research.

Potential Therapies using Stem Cells

Adult Stem Cell Therapies

Bone marrow and peripheral blood stem cell transplants have been utilized for over 40 years as therapy for blood disorders such as leukemia and lymphoma, amongst many others. Scientists have also shown that stem cells reside in most tissues of the body and research continues to learn how to identify, extract, and proliferate these cells for further use in therapy. Scientists hope to yield therapies for diseases such as type I diabetes and repair of heart muscle following heart attack.

Scientists have also shown that there is potential in reprogramming ASCs to cause them to transdifferentiate (turn back into a different cell type than the resident tissue it was replenishing).

Embryonic Stem Cell (ESC) Therapies

There is potential with ESCs to treat certain diseases in the future. Scientists continue to learn how ESCs differentiate and once this method is better understood, the hope is to apply the knowledge to get ESCs to differentiate into the cell of choice that is needed for patient therapy. Diseases that are being targeted with ESC therapy include diabetes, spinal cord injury, muscular dystrophy, heart disease, and vision/hearing loss.

Induced Pluripotent Stem Cell Therapies

Therapies using iPSCs are exciting because somatic cells of the recipient can be reprogrammed to en ESC like state. Then mechanisms to differentiate these cells may be applied to generate the cells in need. This is appealing to clinicians because this avoids the issue of histocompatibility and lifelong immunosuppression, which is needed if transplants use donor stem cells.

iPS cells mimic most ESC properties in that they are pluripotent cells, but do not currently carry the ethical baggage of ESC research and use because iPS cells have not been able to be manipulated to grow the outer layer of an embryonic cell required for the development of the cell into a human being.

Pros and Cons of Using Various Stem Cells

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What are Stem Cells? - University of Nebraska Medical Center

The focus of our work is really to understand the regeneration of the skin and the hair. Michelle Rathman-Josserand, LOral Research Associate, Biologist

BRUNO BERNARD LORAL FELLOW

Franoise BERNERD LOral Fellow

Eva BESSAC LOral Expert in scientific computing

Jonathan GAWTREY LOral, Chemist

VALRIE JEANNE-ROSE LORAL, MATERIAL CHEMIST

ANA MARIA PENA LORAL, BIOPHYSICIST

MICHEL PHILIPPE LORAL RESEARCH ASSOCIATE

Jean-Christophe BICHON LORAL, CHEMIST, EXPERT IN ROBOTICS

Guive BALOOCH LORAL, DIRECTOR OF THE CONNECTED BEAUTY INCUBATOR

CYRIL SWEETLOVE L'ORAL, RESEARCH ENGINEER, ENVIRONMENTAL RESEARCH

CYRIL SWEETLOVE L'ORAL, RESEARCH ENGINEER, ENVIRONMENTAL RESEARCH

CYRIL SWEETLOVE L'ORAL, RESEARCH ENGINEER, ENVIRONMENTAL RESEARCH

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Skin stem cells-LOral Group

Summary

In mammalian skin, multiple types of resident cells are required to create a functional tissue and support tissue homeostasis and regeneration. The cells that compose the epithelial stem cell niche for skin homeostasis and regeneration are not well defined. Here, we identify adipose precursor cells within the skin and demonstrate that their dynamic regeneration parallels the activation of skin stem cells. Functional analysis of adipocyte lineage cells in mice with defects in adipogenesis and in transplantation experiments revealed that intradermal adipocyte lineage cells are necessary and sufficient to drive follicular stem cell activation. Furthermore, we implicate PDGF expression by immature adipocyte cells in the regulation of follicular stem cell activity. These data highlight adipogenic cells as skin niche cells that positively regulate skin stem cell activity, and suggest that adipocyte lineage cells may alter epithelial stem cell function clinically.

Resident skin adipocytes regenerate de novo in parallel with the hair cycle Immature adipocytes are necessary and sufficient for hair follicle regeneration Immature adipocytes express PDGF ligands to promote hair regeneration

Tissue niches are essential for controlling stem cell self-renewal and differentiation (Voog and Jones, 2010). Epithelial lineages in the skin are maintained by stem cells that exist in multiple tissue microenvironments (Blanpain and Fuchs, 2006). In particular, the niche for hair follicle stem cells, which reside within the bulge region of the hair follicle, promotes continual and repetitive regeneration of the follicle during the hair cycle. Specialized mesenchymal cells, the dermal papillae (DP), that are associated with the hair follicle can specify epithelial identity, and are thought to control follicular stem cell activity by releasing signaling molecules (Blanpain and Fuchs, 2006, Greco etal., 2009andRendl etal., 2005). Extrinsic signals, such as bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), platelet derived growth factors (PDGFs) and Wnts can activate stem cell activity in the hair follicle (Blanpain and Fuchs, 2006, Greco etal., 2009andKarlsson etal., 1999). Yet, it remains unclear which cells establish the skin stem cell niche.

Multiple changes within the skin occur during the hair follicle's regenerative cycle (Blanpain and Fuchs, 2006). Following hair follicle morphogenesis (growth phase, anagen), the active portion of the follicle regresses (death phase, catagen), leaving the bulge region with a small hair germ that remains dormant during the resting phase (telogen) (Greco etal., 2009). Anagen induction in the next hair cycle is associated with bulge cell migration and proliferation in the hair germ to generate the highly proliferative cells at the base of the follicle (Greco etal., 2009andZhang etal., 2009). The activated stem cells then differentiate to form the inner root sheath and hair shaft for the new hair follicle.

During activation of hair growth, the expansion of the intradermal adipocyte layer in the skin doubles the skin's thickness (Butcher, 1934, Chase etal., 1953andHansen etal., 1984). The growth of the intradermal adipose depot could occur through adipocyte hypertrophy or adipogenesis. While adipocyte hypertrophy involves lipogenesis, adipogenesis requires the proliferation and specification of adipocyte precursor cells into preadipocytes, which exit from the cell cycle and differentiate into mature, lipid-laden adipocytes (Rodeheffer etal., 2008andRosen and Spiegelman, 2000). Adipogenesis requires the upregulation and transcriptional activity of the nuclear receptor, PPAR in preadipoctyes (Rosen and Spiegelman, 2000), which can be blocked by specific antagonists, bisphenol A diglycidyl ether (BADGE) and GW9662 (Bendixen etal., 2001andWright etal., 2000). Whether intradermal adipocytes undergo hypertrophy and/or adipogenesis during the hair cycle is unknown.

Recent data shows that during the hair cycle, mature intradermal adipocytes express BMP2 mRNA ( Plikus etal., 2008), an inhibitory signal for bulge cell activity ( Blanpain and Fuchs, 2006andPlikus etal., 2008). In addition, reduced intradermal adipose tissue in transgenic mice overexpressing human apolipoprotein C-I in the skin (Jong etal., 1998), fatty acid transport protein (FATP)-4-deficient mice ( Herrmann etal., 2003), and Dgat1/ or Dgat2/ mice ( Chen etal., 2002andStone etal., 2004) results in abnormalities in skin structure and function such as hair loss, epidermal hyperplasia, and abnormal sebaceous gland function. While these data suggest a regulatory role for adipocytes in the skin, these mutations affect multiple cell types in the skin. Thus, the precise role of intradermal adipocytes in skin biology remains unclear.

In this study, we analyze the role of intradermal adipocytes on follicular stem cell activity. Using histological and functional analysis of cell populations of the adipocyte lineage in the skin, we identify a dynamic process of adipogenesis that parallels the activation of hair follicle stem cells. Functional analysis of adipocyte lineage cells in mice with defects in adipogenesis and in transplantation experiments revealed that immature adipocyte cells are necessary and sufficient to drive follicular stem cell activation. Finally, we implicate PDGF signals produced by immature intradermal adipocyte lineage cells in controlling hair regeneration. These data define active roles for intradermal adipocytes in the regulation of the skin tissue microenvironment.

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Adipocyte Lineage Cells Contribute to the Skin Stem Cell ...

Have you noticed signs of aging in your skin? Do you have more dullness, dryness, wrinkles, or sagging than you did five, ten, or fifteen years ago?

If so, youre not alone. All of us experience the aging process, which includes thinning, age spots, loss of strength and elasticity, and increased dryness because of reduced oil production. Most of us dont like the idea of showing our age soweseek solutions to help slow down and conceal the signs of aging on the skin. Though we already have some key tools to use in our fight against the aging process, including natural oils that deeply moisturize, essential fatty acids that plump and firm, and nutrients that help protect from outside elements, science has zoomed in on another powerful anti-aging ally: the stem cell.

At Annmarie Gianni Skin Care, were excited to talk about stem cells because weve found the perfect source to add to our Repair Serum. They come from a clean, natural, and environmentally friendly source and have been shown to help stimulate regeneration and repair on a cellular level for a smoother, tighter, more youthful complexion.

Plant stem cells can help stimulate skin to regenerate and repair itself.

Youve probably heard about stem cells in the news. Most of the media coverage has been about embryonic stem cells because of the controversial sources for these cells the truly amazing scientific discoveries using stem cells are totally overshadowed. Embryonic stem cells have the capacity to form any type of tissue in the body and because of that, they can regenerate failing organs and they are instrumental in working with degenerative diseases.

The adult body has stem cells too but they are a lot more limited than the embryonic stem cells. Adult stem cells are specific to the type of organ that theyre helping to repair and they are limited in what theyre able to restructure in the body. That means that if you have a deep scratch on your skin, the stem cells in your skin would work to repair it but the stem cells in your brain wouldnt be able to migrate to the skin. Adult stem cells are used to regenerate and repair the tissues in the body but they dont have the capacity to regenerate organs the way that embryonic stem cells do (if you lose an arm you cant grow it back, right?).

That being said, the skin is one of the primary locations where we see stem cells at work because the skin is constantly regenerating itself to protect the body from foreign substances. There are a few different types of stems cells that are specific to the integumentary system but the primary stem cell is the epidermal stem cells that are found in the deepest part of the epidermis layer of the skin.

Skin cells have a huge job to do. According to a study published in 2003, the outer layer of skin is always renewing and repairing itself by constant proliferation of a single inner layer of rapidly dividing progeny of stem cells. A more recent study published in 2012 found the existence of a new population of stem cells that give rise to progenitor cells that ensure the daily maintenance of the epidermis [outer layer] and demonstrate the major contribution of epidermal stem cells during wound healing.

Have you noticed that a babys skin can heal really quickly from even the deepest gashes without scarring? Thats a sign of new stem cells that are capable of complete repair. Contrast that with the last time your furry friend loved you a little too much and scratched your leg, how long did that take you heal? Did you scar?

As we age, we encounter the elements and things like sun damage, environmental pollutants, physical damage, and just general decrease in regeneration can weaken and reduce the skins supply of key stem cells. That means skin renewal slows down so if you have noticed that your skin doesnt appear as dewy or young-looking and youre not healing quite as quickly as you used to dont worry, its normal.

Finding help from the plant world is not new for us. All of our products already use the power of plants to help protect and restore the skin but were always looking for ways to make it more effective. We went looking for safe ways to encourage skin repair and regeneration and we werent surprised to find plant stem cells and learn about the amazing effects they can have on the skin.

A plants extra store of stem cells is why they are able to grow new leaves in the spring and how they continue to sprout new life and be a mature entity at the same time. Because plants cannot escape the danger around them, it has been argued that their stem cells may be even stronger than our own, capable of withstanding all types of environmental stress to continue to regenerate and restore the plants various systems throughout its lifetime.

But can plant stem cells really help our human stem cells? Research shows they can. It isnt that the stem cells from plants can regenerate our own stem cells, what the plant stem cells can do however, is protect our own skin cells so they live longer and they stimulate the renerative activity in our own stem cells.

What does that mean to you? Younger looking and acting skin!

In seeking out a source of stem cells for our Repair Serum, we wanted something that wouldnt be irritated for the skin. Thats why when we saw the tests behind citrus stem cells, we were convinced they were the right ones for our customers. Not only are they from a non-human and non-animal source, but they have solid studies behind them.

Here are some of the results that citrus-based stem cells were able to create on the skin:

Do you suffer from skin damage? Please share your story.

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citrus-derived stem cells - Annmarie Gianni Skin Care

The skin cell gun, also known as the skin gun or SkinGun, is a medical device that sprays a patient's own self-donated (autologous) stem cells to treat burns and other wounds. The skin gun is used in conjunction with a technique that isolates adult stem cells from a postage stamp-sized sample of the patient's own skin for application to the wound site, where they differentiate into normal skin. This treatment can replace conventional methods of treating severe wounds, such as skin grafting. Studies demonstrate that damaged skin tissue regenerates after skin gun treatment significantly more quickly than after traditional treatment methods. [1][2][3]

The skin gun, along with related cell isolation methodologies, were acquired by RenovaCare, Inc. in 2013.[4] The company continues to develop the technology and treatment protocol for commercial distribution, under the brand names SkinGun and CellMist System respectively. RenovaCare is also exploring opportunities to apply its SkinGun treatments to additional indications, including chronic wounds, pigmentation disorders, and cosmetic applications. [5]

Stem cells from a postage stamp-sized sample of the patient's healthy skin are isolated using a enzymatic tissue processing protocol. The resulting cell suspension is then transferred to a sterile syringe, which is then inserted into the skin gun. Using its unique spray mechanism, the gun uniformly distributes cells directly into the wound. The newly introduced stem cells begin to migrate, multiply, and differentiate, creating new skin tissue in a matter of days.

The entire process from collecting the skin sample, processing it into a cell suspension, and using the skin gun to spray the stem cells takes approximately 1.52 hours from start to finish. Full re-epithelialization can occur in as little as four days, and after a few months the skin will regain its color and texture.[6][7]

Early experimental versions of the device were developed by Dr. Jrg Gerlach and StemCell Systems GmbH in Berlin, Germany. Dr. Gerlach and SCS had already developed cell culture bioreactors for culturing usable liver and other solid organ tissues from stem cells, and were seeking a similar platform to culture living skin. They soon discovered that, compared to other organs, the skin is a special case. A skin wound is itself an accessible environment that provides excellent conditions to culture new skin tissue in vivo. This solves the problems of wait times and special challenges in transplanting delicate, cultured tissue inherent to in vitro skin culture technologies.[8]

Researchers developed novel stem cell isolation techniques that maximize stem cell availability for transplantation.[9] To ensure minimal loss in transplanting the isolated cells, engineers at StemCell Systems designed a deposition device, the skin gun, to gently deliver the cell suspension without exposing cells to harsh forces in conventional spray devices.[9]

The skin gun method was first used experimentally at Charit Universittsmedizin Berlin on a group of nineteen patients. The clinician in that study determined that the results from the skin gun treatment was so significantly better than traditional grafting that he discontinued performing skin grafts on a control group on the basis of medical ethics.[1]

Subsequently several skin gun procedures have been performed at UPMC Mercy Hospital in Pittsburgh, including patients who have been able to leave hospital within four days of treatment.[3]

After an abrasion, cut, burn, or other injury, the body uses several different of biological processes to repair the skin.[10] Wound healing generally has three different stages: the inflammatory stage, the proliferative stage and the remodeling stage.[11]

Once the skin is damaged, a series of interrelated events take place in close succession in order to repair the skin.[12] Within minutes after an injury occurs, blood platelets collect at the site of injury to form a clot. This clot limits bleeding at the injury site.

The inflammatory phase involves increased white blood cell activity, removing bacteria and debris from the wound. Biochemical signals instruct regenerative cells to begin dividing, to create new skin tissues much more rapidly than normal.

The proliferative phase is marked by the formation of new skin tissue at the injury site and the general shrinking and eventual disappearance of the wound.[13] New blood vessels are also established during the healing process. The wound is made smaller by myofibroblasts, which hold on to the edges of the wound and slowly get smaller by a system similar to the contraction of muscle cells.

During the remodeling phase, the skin acquires its permanent texture and unneeded cells are disposed of through apoptosis.

To date skin gun treatment has been used exclusively with second degree burns, though there is strong evidence that the treatment will be successful in treating a variety of skin wounds and skin disorders. Patients with infected wounds or with delay in wound healing are suitable for cell grafting treatment.[3] Third-degree burns, however, completely deprive victims of both their epidermis and dermis skin levels, which exposes the tissue surrounding the muscles. The skin gun has not progressed to the point where it can be used for such advanced wounds, and these patients must seek more traditional treatment methods. The skin gun is generally not used for burn victims with anything less than a second-degree burn either. First degree-burns still maintain portions of the epidermis and can readily heal on their own, thus they do not need this expensive technology.

Currently, the skin gun's applications have not been extended to include the regeneration of skin lost due to other injuries or skin diseases. It is also limited in that it is only effective immediately following the burn incident.[14]

The average healing time for patients with second degree burns is three to four weeks.[15] This is reduced to a matter of days with skin gun treatment.[1][2][3]

Traditional skin grafting can be risky, in that chances for infection are relatively high. The skin gun alleviates this concern because the increased speed in which the wound heals directly correlates to the decreased time the wound can be vulnerable to infection. Because of the rapid re-epithelialization associated with skin gun treatment, harmful side effects that can result from an open wound are significantly reduced.[16] Applying the skin cells is quick and doesn't harm the patient because only a thin layer of the patients healthy skin is extracted from the body into the aqueous spray. The electronic spray distributes the skin cells uniformly without damaging the skin cells, and patients feel as if they are sprayed with salt water.[16]

Because the skin cells are actually the patients own cells, the skin that is regenerated looks more natural than skin grown from traditional methods. During recovery, the skin cells grow into fully functional layers of the skin, including the dermis, epidermis, and blood vessels.[17] The regenerated skin leaves little scarring. The basic idea of optimizing regenerative healing techniques to damaged biological structures demonstrated by the skin gun in the future may also be applied to engineering reconstruction of vital organs, such as the heart and kidneys.[17]

There are major limitations: the method will not work on deep burns that go through bone and muscle, specifically below the dermis. As of 2011, only several dozen patients have been treated; it remains an experimental, not a proven, method. As of 2011, the skin gun was still in its prototyping stage, since it has only treated a dozen patients in Germany and the US, compared to over 50,000 treated with Dermagraft bioengineered skin substitute. There is thus a lack of published peer reviewed clinical evidence, and no knowledge of long-term stability of the newly generated skin.

The skin gun has been featured in numerous books and television shows, including the following examples.

Continue reading here:
Skin cell gun - Wikipedia, the free encyclopedia

Presented at the 8th World Congress for Hair Research (2014) Jeju Island, South Korea.

Understanding molecular mechanisms for regeneration of hair follicles during wound healing provides new opportunities for developing treatments for hair loss and other skin disorders. We show that fibroblast growth factor 9 (fgf9) modulates hair follicle regeneration following wounding of adult mice. Inhibition of fgf9 during wound healing severely impedes this wound-induced hair follicle neogenesis (WIHN). Conversely, overexpression of fgf9 results in a 2-3 fold increase in the number of neogenic hair follicles. Remarkably, gamma-delta T cells in the wound dermis are the initial source of fgf9. Deletion of fgf9 gene in T cells in Lck-Cre;floxed fgf9 results in a marked reduction in WIHN. Similarly, mice lacking gamma-delta T cells demonstrate impaired follicular neogenesis.

We found that fgf9, secreted by gamma-delta T cells, initiates a regenerative response by triggering Wnt expression and subsequent Wnt activation in wound fibroblasts. Employing a unique feedback mechanism, activated fibroblasts then express fgf9, thus amplifying Wnt activity throughout the wound dermis during a critical phase of skin regeneration. Strikingly, humans lack a robust population of resident dermal gamma-delta T cells, potentially explaining their inability to regenerate hair.

These findings which highlight the essential relationship between the immune system and tissue regeneration, establish the importance of fgf9 in hair follicle regeneration and suggests its applicability for therapeutic use in humans.

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Dr George Cotsarelis: Hair Follicle Stem Cells & Skin ...

Presented at the 8th World Congress for Hair Research (2014) Jeju Island, South Korea.

Understanding molecular mechanisms for regeneration of hair follicles during wound healing provides new opportunities for developing treatments for hair loss and other skin disorders. We show that fibroblast growth factor 9 (fgf9) modulates hair follicle regeneration following wounding of adult mice. Inhibition of fgf9 during wound healing severely impedes this wound-induced hair follicle neogenesis (WIHN). Conversely, overexpression of fgf9 results in a 2-3 fold increase in the number of neogenic hair follicles. Remarkably, gamma-delta T cells in the wound dermis are the initial source of fgf9. Deletion of fgf9 gene in T cells in Lck-Cre;floxed fgf9 results in a marked reduction in WIHN. Similarly, mice lacking gamma-delta T cells demonstrate impaired follicular neogenesis.

We found that fgf9, secreted by gamma-delta T cells, initiates a regenerative response by triggering Wnt expression and subsequent Wnt activation in wound fibroblasts. Employing a unique feedback mechanism, activated fibroblasts then express fgf9, thus amplifying Wnt activity throughout the wound dermis during a critical phase of skin regeneration. Strikingly, humans lack a robust population of resident dermal gamma-delta T cells, potentially explaining their inability to regenerate hair.

These findings which highlight the essential relationship between the immune system and tissue regeneration, establish the importance of fgf9 in hair follicle regeneration and suggests its applicability for therapeutic use in humans.

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Dr George Cotsarelis: Hair Follicle Stem Cells & Skin ...

We observed similar stem cell plasticity when we purified and tested the myoepithelial stem cells from sweat glands (Lu et al., 2012; Blanpain and Fuchs, 2014). Similar to myoepithelial stem cells of mammary glands, these stem cells normally act unipotently and only replenish dying myoepithelial cells of the gland. However, when purified by fluorescence activated cell sorting (FACS) and transplanted directly into a mammary fat pad, the stem cells can regenerate the complete bi-layered gland, and the new luminal cells secrete sweat. Moreover, when engrafted to the skin, these stem cells can make epidermis. An area of interest in my lab is to understand the environmental cues that dictate the fascinating plasticity of epithelial stem cells, and to elucidate the chromatin remodeling that leads to the changes in gene expression necessary to generate different tissues from a common progenitor.

To understand how a stem cell chooses its differentiation pathway, we have taken several approaches. An ongoing approach of the lab is to express different fluorescent proteins under the control of various skin promoters, active at different stages in stem cells and their lineages. Through FACS, we've purified cells at different time points along the lineages and generated a battery of lineage-specific profiles, enabling us to define at an mRNA (RNA-seq) and chromatin (ChIP-seq) level how stem cells change as they transition from quiescence to activation to lineage determination. Our global objective is to exploit this information to understand how stem cells receive signals, change their program of gene expression and select a lineage. We also want to understand the functional significance of these changes. The beauty of the hair follicle as a model is that it is currently the only system where sufficient quantities of stem cells can be isolated directly from their native niche in order to carry out whole-genome wide analyses in vivo. This eliminates the caveats arising from culturing cells, namely induction of a stress response and large-scale epigenetic changes in gene expression.

For the hair follicle, >150 mRNAs are selectively upregulated in the bulge stem cells relative to their short-lived progeny (Tumbar et al., 2004; Blanpain et al., 2004; Keyes et al., 2013). A number of these changes are in transcription factors and epigenetic regulators. Weve conducted in vivo chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) on chromatin from hair follicle stem cells (HFSCs) and their short-lived progeny. Bioinformatics reveals which genes bind these transcription factors, and how this changes as the stem cells progress to form transiently dividing cells that then terminally differentiate along one of the 7 distinct concentric cell layers that constitute the hair and its channel. By conducting high throughput RNA sequencing (RNA-seq) on HFSCs lacking each of these genes, weve learned which target genes depend upon binding these transcription factors. Finally, by engineering inducible-conditional knockouts to selectively remove these transcription factors in the stem cells, weve learned the physiological relevance of these factors.

Based upon these analyses, TCF3/TCF4, LHX2 and SOX9 are all essential for maintaining the hair follicle stem cells in their native niche (Nguyen et al., 2006; 2009; Rhee et al., 2006; Folgueras et al., 2013; Lien et al., 2011; 2014; Nowak et al., 2008; Kadaja et al., 2014). In addition, LHX2 represses sebaceous gland differentiation: following its loss, the stem cell niche soon becomes a sebaceous gland (Folgueras et al., 2013). SOX9 represses epidermal differentiation: following its loss, the niche becomes an epidermal cyst (Kadaja et al., 2014). TCF3 and TCF4 repress HF differentiation: following their loss, quiescent HFSCs precociously activate a new hair cycle (Lien et al., 2014). TCF3 and TCF4 can partner with -catenin, which is stabilized and becomes nuclear upon Wnt signaling: if -catenin is silenced in the quiescent HFSCs, they never reenter a new hair cycle. In their native niche, quiescent HFSCs express a transcriptional repressor TLE4 which binds to TCF3 and TCF4: our findings are consistent with the view that Wnt signaling functions by relieving TCF3/4/TLE4-mediated repression (Lien et al., 2014).

NFATc1 is required for maintaining HFSC quiescence, and in its absence, HFs cycle precociously (Horsley et al., 2008). Additionally, NFATc1 is downstream of BMP signaling, offering a potential explanation as to why BMP signaling must be lowered to activate hair cycling. A major feature of the aging HFSC signature is elevated NFATc1 target genes, and we can stimulate old follicles by inhibiting NFATc1 (Keyes et al., 2013). A major question still to be answered is whether HFSCs have an endless capacity for hair cycling and whether this same phenomenon operates in aging scalp hairs in humans. If so, these findings may open new doors for future therapeutics.

NFiB is a transcription factor which is specific to the HFSCs, but functions by repressing the expression of genes that are essential for the differentiation of the melanocyte stem cells, which reside within the same stem cell niche (Chang et al., 2013). These two stem cell populations must be activated at the same time so that differentiating melanocytes can transfer pigment to the differentiating hair cells to provide the natural coloring to our hair. Loss of NFiB uncouples this crosstalk and leads to the precocious activation of a key NFiB target gene that encodes a secreted melanocyte differentiation factor (Chang et al., 2013).

There are a number of additional transcription factors and epigenetic regulators which are enhanced in the complex milieu of HF stem cell chromatin, and there is still much to be learned. Of the epigenetic regulators, weve thus far examined only the role of polycomb chromatin repressor complexes, which weve shown function critically in controlling the fate switch from a stem cell to a committed, transit-amplifying state (Ezhkova et al., 2009; 2011; Lien et al., 2011). In coming years, we will continue to systematically work our way through the functional significance and mechanism of action of epigenetic and transcriptional controls on stem cells as they transit from a quiescent to activated to committed state. When coupled with our recent ability to efficiently knockdown genes in a few days using lentiviral-mediated shRNA delivery (Beronja et al., 2010), this now becomes a powerful tool for exploiting bioinformatics analyses to gain biological insights.

Our ultimate goal is to understand how external signals from the surrounding niche microenvironment impact chromatin dynamics to achieve tissue production. Equally important will be the expression of specific genes that enables them to remodel their cytoskeleton and adhesive contacts and either form a stratified epidermis or an epithelial bud that can then develop into a hair follicle (Perez-Moreno et al., 2003; Blanpain and Fuchs, 2009; Hsu et al., 2014). While our model is the skin, the problem is a general one of how a single epithelial stem cell gives rise to a spatially organized, functional tissue. It is also integrally linked to understanding the basis of cancer progression.

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The Rockefeller University Stem Cells of the Skin and ...

05/15/13Portland, Ore.

The breakthrough marks the first time human stem cells have been produced via nuclear transfer and follows several unsuccessful attempts by research groups worldwide

Update 05/23/2013: OHSU releases statement on questions about photos in stem cell paper. Read the statement.

Scientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. It is believed that stem cell therapies hold the promise of replacing cells damaged through injury or illness. Diseases or conditions that might be treated through stem cell therapy include Parkinsons disease, multiple sclerosis, cardiac disease and spinal cord injuries.

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. This latest research will be published in the journal Cell online May 15 and in print June 6.

The technique used by Drs. Mitalipov, Paula Amato, M.D., and their colleagues in OHSUs Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, is a variation of a commonly used method called somatic cell nuclear transfer, or SCNT. It involves transplanting the nucleus of one cell, containing an individuals DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.

A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells. Furthermore, because these reprogrammed cells can be generated with nuclear genetic material from a patient, there is no concern of transplant rejection, explained Dr. Mitalipov. While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine.

Another noteworthy aspect of this research is that it does not involve the use of fertilized embryos, a topic that has been the source of a significant ethical debate.

The Mitalipov teams success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs showed that human egg cells appear to be more fragile than eggs from other species. Therefore, known reprogramming methods stalled before stem cells were produced.

To solve this problem, the OHSU group studied various alternative approaches first developed in monkey cells and then applied to human cells. Through moving findings between monkey cells and human cells, the researchers were able to develop a successful method.

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OHSU research team successfully converts human skin cells ...