Archive for the ‘Skin Stem Cells’ Category

Harvard scientists have merged stem cell and organ-on-a-chip technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine because it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

The work, published in May 2014 in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Children's Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

A release from Harvard explains that using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients. The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease. The release quotes Parker as saying, "You don't really understand the meaning of a single cell's genetic mutation until you build a huge chunk of organ and see how it functions or doesn't function. In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think that's a big advance."

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract. "The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROSa normal byproduct of cellular metabolism released by mitochondriawhich had not been recognized as an important part of this disease," said Pu, who cares for patients with the disorder. "We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function," Pu added. "Now, whether that can be achieved in an animal model or a patient is a different story, but if that could be done, it would suggest a new therapeutic angle." His team is now trying to translate this finding by doing ROS therapy and gene replacement therapy in animal models of Barth syndrome to see if anything could potentially help human patients. At the same time, the scientists are using their human 'heart disease-on-a-chip' as a testing platform for drugs that are potentially under trial or already approved that might be useful to treat the disorder.

"We tried to thread multiple needles at once and it certainly paid off," Parker said. "I feel that the technology that we've got arms industry and university-based researchers with the tools they need to go after this disease." Both Parker and Pu, who first talked about collaborating at a 2012 Stockholm conference, credit their partnership and scientific consilience for the success of this research. Parker asserted that the 'organs-on-chips' technology that has been a flagship of his lab only worked so fast and well because of the high quality of Pu's patient-derived cardiac cells. "When we first got those cells down on the chip, Megan, one of the joint first authors, texted me 'this is working,'" he recalled. "We thought we'd have a much harder fight." "When I'm asked what's unique about being at Harvard, I always bring up this story," Pu said. "The diverse set of people and cutting-edge technology available at Harvard certainly made this study possible." The researchers also involved in this work include: Joint first authors Gang Wang, MD, of Boston Children's Hospital, and Megan McCain, PhD, who earned her degree at the Harvard School of Engineering and Applied Sciences and is now an assistant professor at the University of Southern California. Amy Roberts, MD, of Boston Children's Hospital, and Richard Kelley, MD, PhD, at the Kennedy Krieger Institute provided patient data and samples, and Frdric Vaz, PhD, and his team at the Academic Medical Center in the Netherlands conducted additional analyses. Technical protocols were shared by Kenneth Chien, MD, PhD, at the Karolinska Institutet.

Kevin Kit Parker, PhD, is the Tarr Family Professor of Bioengineering and Applied Physics in Harvard's School of Engineering and Applied Sciences, a Core Faculty member of the Wyss Institute for Biologically Inspired Engineering, and a Principal Faculty member of the Harvard Stem Cell Institute. William Pu, MD, is an Associate Professor at Harvard Medical School, a member of the Department of Cardiology at Boston Children's Hospital, and an Affiliated Faculty member of the Harvard Stem Cell Institute. George Church, PhD, is a Professor of Genetics at Harvard Medical School and a Core Faculty member of the Wyss Institute of Biologically Inspired Engineering. The work was supported by the Barth Syndrome Foundation, Boston Children's Hospital, the National Institutes of Health, and charitable donations from Edward Marram, Karen Carpenter, and Gail Federici Smith.

See the original post here:
Stem Cells Make Heart Disease-on-a-Chip

Image Caption: Researchers use modified RNA transfection to correct genetic dysfunction in heart stem cells derived from Barth syndrome patients. The series of images show how inserting modified RNA into diseased cells causes the cells to produce functioning versions of the TAZ protein (first image: in green) that correctly localize in the mitochondria (second image: in red). When the images are merged to demonstrate this localization, green overlaps with red, giving the third image a yellow color. Credit: Gang Wang and William Pu/Boston Children's Hospital

[ Watch The Video: Cardiac Tissue Contractile Strength Differences Shown Using Heart-On-A-Chip ]

Harvard University

Harvard scientists have merged stem cell and organ-on-a-chip technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine, as it is working proof that a chunk of tissue containing a patients specific genetic disorder can be replicated in the laboratory.

The work, published in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Childrens Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients.

The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease.

You dont really understand the meaning of a single cells genetic mutation until you build a huge chunk of organ and see how it functions or doesnt function, said Parker, who has spent over a decade working on organs-on-chips technology. In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think thats a big advance.

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didnt seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cells ability to build itself in a way that allows it to contract.

Original post:
'Heart Disease-On-A-Chip' Made From Patient Stem Cells

Eczema is one of the most common skin conditions, affecting up to 30% of people in the US. Symptoms include dry, itchy skin and rashes. But according to new research, having eczema may not be all that bad; it could reduce the risk of skin cancer.

In a study published in the journal eLife, researchers from Kings College London in the UK say that eczema, also known as atopic dermatitis, activates an immune response that sheds potentially cancerous cells from the skin, preventing tumor formation.

According to the research team, including Prof. Fiona Watt of the Centre for Stem Cells and Regenerative Medicine at Kings College, previous studies have suggested that eczema may reduce the risk of skin cancer.

However, they note that this association has proven difficult to confirm in human studies, as medication for eczema may influence cancer risk. Furthermore, symptoms of the condition vary in severity in each individual.

Eczema reduced tumor formation in mice models

For their study, the team genetically engineered mice to have skin defects commonly found in humans with eczema.

They did this by removing structural proteins in the outer layers of their skin, causing them to have an abnormal skin barrier.

The researchers then tested two cancer-causing chemicals in the genetically engineered mice, as well as in normal mice.

They found that the number of benign tumors in defected mice was six times lower than the number found in the normal mice.

Further investigation revealed that although both the defected and normal mice had equal susceptibility to mutations caused by the chemicals, the defected mice had an exaggerated inflammatory response that resulted in potentially cancerous cells being shed from the skin.

See the rest here:
Eczema may reduce skin cancer risk

16 hours ago A signal from Transit-Amplifying Cells (TACs) activates stem cells in the hair follicle, researchers have found. Both types of cells appear in green (top), with TACs clustered lower down. The researchers identified the signal as Sonic Hedgehog. In experiments, such as this one (bottom), they disabled the signal, interfering with hair growth and regeneration.

(Phys.org) Stem cells switch off and on, sometimes dividing to produce progeny cells and sometimes resting. But scientists don't fully understand what causes the cells to toggle between active and quiet states.

New research in Elaine Fuchs' Laboratory of Mammalian Cell Biology and Development focused on stem cells in the hair follicle to determine what switches them on. The researchers found cells produced by the stem cells, progeny known at Transit-Amplifying Cells or TACs, emit a signal that tells quiet hair follicle stem cells to become active.

"Many types of mammalian stem cells produce TACs, which act as an intermediate between the stem cells and their final product: fully differentiated cells in blood, skin and elsewhere," says Ya-Chieh Hsu, who conducted the research while as a postdoc in the lab and will soon move to Harvard University. "In the past, TACs were seen as a population of cells that sat by passively cranking out tissues. No one expected them to play a regulatory role."

Hsu and Fuchs went a step further to identify the signal sent out by the TACs. They pinpointed a cell-division promoting protein called Sonic Hedgehog, which plays a role in the embryonic development of the brain, eyes and limbs.

Stem cells are medically valuable because they have the potential to produce a number of specialized cells suitable for specific roles. Stem cells' production of these differentiated cells is crucial to normal maintenance, growth and repair. Many tissues have two populations of stem cells: one that divides rarely, known as the quiescent stem cells, and another that is more prone to proliferate, known as primed stem cells. Regardless of their proliferation frequency, most stem cells in humans do not directly produce differentiated progeny cells; instead, they give rise to an intermediate proliferating population, the TACs.

The hair follicle, the tiny organ that produces a hair, forms a narrow cavity down into the skin. It cycles between rounds of growth, destruction and rest. When entering the growth phase, the primed stem cell population is always the first to divide and generates the TACs clustered lower down in the hair follicle. Primed stem cell proliferation sets the stage for the next round of hair growth, a process which ensures hairs are replaced as they are lost over time. Proliferating TACs produce the hair shaft, as well as all the cells surrounding the hair underneath the skin, which make up the follicle itself.

At the outset, Hsu and Fuchs suspected a role for both the TACs and for Sonic Hedgehog in hair regeneration.

"We noticed that the primed stem cell population gets activated early and makes the TACs, while the quiescent stem cell population only becomes activated once TACs are generated. This correlation prompted us to look for a signal that is made by the TACs. Sonic Hedgehog is that signal, as we went on to demonstrate," explained Fuchs.

In experiments described this week in Cell, Hsu disabled TACs' ability to produce the Sonic Hedgehog protein by knocking out the gene responsible in the hair follicles of adult mice. As a result, the proliferation of hair follicle stem cells and their TACs are both compromised. They further showed that it is the quiescent stem cell population which requires Sonic Hedgehog directly for proliferation.

See the original post here:
Stem cell progeny tell their parents when to turn on

A study has found that it is possible to convert skin cells into the male germ cells, which are responsible for sperm production in the testes, using an established technique for creating embryonic stem cells using a form of genetic engineering.

The researchers showed that stem cells derived from human skin become active germ cells when transplanted into the testes of mice even when the man suffers from a genetic condition where he lacks functioning germ cells in his own testes.

Creating sperm-producing human cells in laboratory mice will allow scientists to study in more detail the complex sequence of events during the development if the male reproductive tissue, and to understand how these developmental changes can go awry in infertile men.

Our results are the first to offer an experimental model to study sperm development. Therefore, there is potential for applications [such as] cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish, said Renee Reijo Pera of Montana State University.

It might even be possible to transplant stem cell-derived germ cells directly into the testes of men with problems producing sperm, said Professor Reijo Pera, who led the study published in the journal Cell Reports. However, she emphasised that further research will be needed before clinical trials can be allowed on humans.

Although the mice had functioning human male germ cells, they did not produce human sperm, Dr Reijo Pera said. There is an evolutionary block that means that when germ cells from one species are transferred to another, there is not full spermatogenesis, unless the species are very closely related, she explained.

About one in a hundred men suffer from azoospermia, where they fail to produce measurable quantities of sperm in the semen. The condition is responsible for about 20 per cent of cases of male infertility, which itself accounts for about half of the 10-15 per cent of couples who have difficulty conceiving naturally.

The study involved creating induced pluripotent stem cells by adding key genes to the skin cells of five men three with a form of azoospermia caused by a genetic mutation on the Y chromosome and two with normal fertility. The resulting stem cells were implanted into the testes of laboratory mice where they developed normally into germ cells.

The scientists found that even the stem cells derived from the infertile men were capable to developing into human male germ cells in the mouse testes. However, the stem cells of the men with the Y chromosome mutation produced about 100 times less germ cells than the men with normal fertility, Professor Reijo Pera said.

Studying why this is the case will help us to understand where the problems are for these men and hopefully find ways to overcome them, Professor Reijo Pera said.

Link:
New infertility treatment could grow sperm from skin cells

We put up with dry, itchy skin and are constantly applying creams to try (in vain) to fight the flake - but there might be some much needed good news for us eczema sufferers.

New research suggests eczema sufferers may have less chance of developing skin cancer.

A study conducted by experts at King's College London found the immune response triggered by eczema could stop tumours forming by shedding potentially cancerous cells.

Genetically engineered mice lacking three skin proteins - known as "knock-out" mice - were used to replicate some of the skin defects found in eczema sufferers.

Cancer-causing chemicals were tested on normal mice and the knock-out mice. Researchers found the number of benign tumours per mouse was six times lower in knock-out mice.

The new study, published in eLife, suggests both types of mice were equally susceptible to getting cancer-causing mutations, but an exaggerated inflammatory reaction in knock-out mice led to enhanced shedding of potentially cancerous cells from the skin.

Professor Fiona Watt, director of the centre for stem cells and regenerative medicine at King's College London, said: "We are excited by our findings as they establish a clear link between cancer susceptibility and an allergic skin condition in our experimental model.

"They also support the view that modifying the body's immune system is an important strategy in treating cancer.

"I hope our study provides some small consolation to eczema sufferers - that this uncomfortable skin condition may actually be beneficial in some circumstances."

See more here:
Eczema Could Reduce The Risk Of Skin Cancer, Research Shows

A new development in fertility treatment scientists have successfully produced early-stage sperm cells from the skin cells of infertile men.

According to the study, Stanford University researchers took skin cells from infertile men, turned them into stem cells known as induced pluripotent stem cellsand then implanted those cells in the tubules of mice testes. (Via Flickr / 7715592@N03,33852688@N08)

Before we move forward, you might be wondering how scientists turned skin cells back into stem cells. This video from Stem Cell Network sums up the process.

"If some adult cell types are taken, grown in plastic dishes and given specific genetic instructions, over time a small number of these cells will reverse from their differentiated state and develop the ability to redifferentiate."(Via Vimeo /Stem Cell Network)

Researchers discovered the stem cells developed into germ cells, the precursor to sperm cells. (Via YouTube / CreekValleyCritters)

But while this new development seemingly bodes well for future fertility treatment, a writer for The Guardian points out one major concern.

"The cells that lodged in the tubules developed into early-stage sperm cells, but others turned into small tumours. The danger of causing cancer in the men is one of the major risks that scientists need to overcome." (Via The Guardian)

And LiveScience reports the research is still in its infancy, noting even though the stem cells produced germ cells, they "did not go on to form mature sperm in the mice."The head researcher for the study told LiveScience this is likely because of the "evolutionary differences between humans and mice."

Despite concerns, Nature World News says this research has potential, because there are various uses for the treatment. "There is also the possibility of using cells from endangered species to help boost their reproduction."

According to the American Society for Reproductive Medicine, about 12 percentof adults suffer from infertility. The study has been published in the journal Cell Reports.

Read the original post:
Human skin cells used to create sperm cells

Scientists have turned skin tissue from infertile men into early-stage sperm cells in a groundbreaking study that raises hopes for new therapies for the condition.

The unexpected success of the procedure has stunned some scientists, because it was thought to be impossible for the men to make any sperm.

The men who took part in the study had major genetic defects on their Y sex chromosomes, which meant they could not produce healthy adult sperm on their own.

About 1% of men cannot make any sperm, a condition known as azoospermia, while a fifth of men have low sperm counts. Male fertility is a concern for roughly half of couples who seek IVF treatment.

In the latest study, researchers took skin cells from three infertile men and converted them into stem cells, which can grow into almost any tissue in the body. When these cells were transplanted into the testes of mice, they developed into early-stage human sperm cells.

What we found was that cells from men who did not possess sperm at the time of clinical observation were able to produce the precursors for sperm, said Cyril Ramathal, of Stanford University.

Skin cells from infertile men grew into fewer early-stage sperm cells than cells taken from normally fertile men, the study found.

The research is at an early stage, but scientists suspect that the converted skin cells might have grown into mature sperm cells if they had been transplanted into the infertile mens testes.

If further work confirms the suspicion, it may be possible to restore male fertility by taking mens skin cells, turning them into stem cells, and injecting these into their testes. The same might be done for men who are left infertile after having chemotherapy for cancer.

Being able to efficiently convert skin cells into sperm would allow this group to become biologic fathers, said Michael Eisenberg, director of male reproduction and surgery at Stanford, who was not involved in the study. Infertility is one of the most common and devastating complications of cancer treatments, especially for young boys and men.

See original here:
Scientists turn tissue from infertile men into sperm cells

Here is a new development in fertility treatment: Scientists have successfully produced early-stage sperm cells from the skin cells of infertile men.

According to thestudy, Stanford University researchers took skin cells from infertile men, turned them into stem cells known as induced pluripotent stem cells, and then implanted those cells in the tubules of mice testes. (ViaFlickr / 7715592@N03,33852688@N08)

Before we move forward, you might be wondering how scientists turned skin cells back into stem cells. Stem Cell Networksummed up the process: "If some adult cell types are taken, grown in plastic dishes and given specific genetic instructions, over time a small number of these cells will reverse from their differentiated state and develop the ability to redifferentiate."(ViaVimeo /Stem Cell Network)

>> Read more trending stories

Researchers discovered the stem cells developed into germ cells, the precursor to sperm cells. (ViaYouTube /CreekValleyCritters)

But while this new development seemingly bodes well for future fertility treatment, a writer forThe Guardianpoints out one major concern: "The cells that lodged in the (mice) tubules developed into early-stage sperm cells, but others turned into small tumors. The danger of causing cancer in the men is one of the major risks that scientists need to overcome."(ViaThe Guardian)

Despite concerns,Nature World Newssays this research has potential, because there are various uses for the treatment."There is also the possibility of using cells from endangered species to help boost their reproduction," the organization reported.

According to theAmerican Society for Reproductive Medicine, about 12 percentof adults suffer from infertility. The study has been published in the journal Cell Reports.

Read more:
Scientists use human skin to create sperm cells

Skin cells from infertile men can be turned into the precursors of sperm cells in a lab, according to a new study.

The findings raise the possibility of one day making sperm from the skin cells of men with fertility problems, the researchers said. However, much more research is needed to determine if this is possible and whether it is safe.

In the new study, researchers first transformed the men's skin cells into stem cells, then implanted the cells into the testes of mice where they formed sperm precursor cells. However, one safety issue is that some of the stem cells formed tumors in the mice, said study researcher Renee Reijo Pera, who conducted the work while at Stanford University, and is now a professor of cell biology and neurosciences at Montana State University.

To conduct the study, Pera and colleagues took skin samples from three infertile men, and two fertile men. The infertile men had a genetic mutation in a region of the genome called AZF1 that prevented them from making mature sperm, a condition called azoospermia. [Sexy Swimmers: 7 Facts About Sperm]

The researchers used the skin cells to produce what are called induced pluripotent stem cells (iPS cells), which have the ability to become nearly any tissue type in the body. These iPS cells were then implanted into the testes of mice, where they turned into germ cells, which normally give rise to sperm in males.

However, in the study, the germ cells did not go on to form mature sperm in the mice, likely because of evolutionary differences between humans and mice that blocked the production of such mature cells, Pera said.

The stem cells from fertile men were much better at generating germ cells than those from infertile men. Still, the fact that the infertile men's stem cells produced germ cells at all was surprising, because men with the AZF1 mutation often have no germ cells, Pera said.

The new findings suggest that these infertile men do in fact have the potential to produce germ cells, but the germ cells are lost over time, Pera said. If that's true, young boys with this mutation might be able to preserve their germ cells for the future by collecting and freezing samples of testes tissue, Pera said.

The mouse model used in the study will help researchers better understand the earliest stages of sperm development, Pera said. For example, the cells of human embryo "decide" whether they are going to be germ cells at day 12 after conception, she said. "We've developed a way to study the earliest steps," which take place in the fetus, Pera said.

Previously, the same group of researchers created germ cells from human embryonic stem cells. And last year, experiments in mice showed that skin cells of the animals can be turned into stem cells, which can then be turned into germ cells. When researchers implanted these germ cells in sterile mice, the mice became fertile.

Originally posted here:
Skin cells turned into sperm

May 2, 2014 7:02 pm by Stephanie Baum | 0 Comments MedCity News

In the latest stem cell innovation, a group of researchers from Stanford University successfully converted skin cells to stem cells to sperm cells, raising new questions about a potential path to treat infertility. The study was published in Cell Report.

The research used skin samples from five men with a genetic mutation calledazoospermia a genetic mutation that prevented them from making mature sperm.

According to a description of the study on NPRs website, researchers took skin cells from infertile men and transformed them into pluripotent stem cells, which can be converted into any cell in the body. The cells were inserted in mice testes and became immature human sperm cells.

The research is certainly at the early stage and experts caution it will take a lot more research to develop healthy sperm but it is already drawing mixed responses from the research world. Although its been called provocative, Dartmouth bioethicist Ronald Green got particularly dark and called attention to the downside. He speculated that it could lead to thefts of tissue samples or hair from the dead to recreate the dearly departed.

Get our daily newsletter or follow us.

Please enter your email below:

Excerpt from:
Stem cell innovation study converts skin cells to sperm cells in potential infertility treatment

By Estel Grace Masangkay

An independent group of scientists led by experts at the New York Stem Cell Foundation Research Institute (NYSCF) reported that they have manufactured the first disease-specific line of embryonic stem cells made with a patients DNA. The achievement is heralded as a major breakthrough in the regenerative medicine field.

This is also the first time cloning technologies have been utilized to generate genetically matched stem cells. The team used somatic cell nuclear transfer to successfully clone a skin cell from a 32 year old female patient with Type 1 diabetes. The cells were transformed into insulin-producing cells similar to lost beta cells in diabetes, which could provide better treatment or even a cure for T1D.

Susan Solomon, CEO and co-founder of NYSCF, says she is excited about the successful production of patient-specific stem cells using somatic cell nuclear transfer (SCNT). CEO Solomon said she became involved with medical research when her son was diagnosed with T1D.

Dr. Egli, scientist from the New York Stem Cell Foundation Research Institute and who led the research, said, From the start, the goal of this work has been to make patient-specific stem cells from an adult human subject with type-1 diabetes that can give rise to the cells lost in the disease. By reprograming cells to a pluripotent state and making beta cells, we are now one step closer to being able to treat diabetic patients with their own insulin-producing cells.

The scientists analyzed factors that affect stem-cell derivation after SCNT. They added histone deacetylase inhibitors and protocol for human oocyte activation, which were crucial in delivering them to the stage at which embryonic stem cells can be properly derived. The beta cells produced from the patients own skin cells are autologous and match the patients DNA. Further research is underway at NYSCF and other institutions for the development of strategies to protect existing and therapeutic beta cells from attacks of the immune system.

The research teams work appeared in the journal Nature.

See the original post:
Scientists Produce Personalized Stem Cells For Specific Diseases

hide captionNew research could be promising for infertile men. Scientists were able to make immature sperm cells from skin cells. Their next challenge is to make that sperm viable.

New research could be promising for infertile men. Scientists were able to make immature sperm cells from skin cells. Their next challenge is to make that sperm viable.

Scientists reported Thursday they had figured out a way to make primitive human sperm out of skin cells, an advance that could someday help infertile men have children.

"I probably get 200 emails a year from people who are infertile, and very often the heading on the emails is: Can you help me?" says Renee Reijo Pera of Montana State University, who led the research when she was at Stanford University.

In a paper published in the journal Cell Reports, Pera and her colleagues describe what they did. They took skin cells from infertile men and manipulated them in the laboratory to become induced pluripotent stem cells, which are very similar to human embryonic stem cells. That means they have the ability to become virtually any cell in the body.

They then inserted the cells into the testes of mice, where they became very immature human sperm cells, the researchers report.

"It's much easier than we actually expected," Pera told Shots.

Other researchers caution that there's still much more research that is needed to prove these cells would actually become healthy sperm that could make a baby. But they said the report was intriguing.

"It's one step closer to being able to make sperm in a petri dish," says George Daley, a stem-cell researcher at Harvard. "So I think that's very provocative."

But others worry the techniques could be misused.

Visit link:
'Provocative' Research Turns Skin Cells Into Sperm

PUBLIC RELEASE DATE:

1-May-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Stem cells made from the skin of adult, infertile men yield primordial germ cells cells that normally become sperm when transplanted into the reproductive system of mice, according to researchers at the Stanford University School of Medicine and Montana State University.

The infertile men in the study each had a type of genetic mutation that prevented them from making mature sperm a condition called azoospermia. The research suggests that the men with azoospermia may have had germ cells at some point in their early lives, but lost them as they matured to adulthood.

Although the researchers were able to create primordial germ cells from the infertile men, their stem cells made far fewer of these sperm progenitors than did stem cells from men without the mutations. The research provides a useful, much-needed model to study the earliest steps of human reproduction.

"We saw better germ-cell differentiation in this transplantation model than we've ever seen," said Renee Reijo Pera, PhD, former director of Stanford's Center for Human Embryonic Stem Cell Research and Education. "We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages."

Unlike many other cellular and physiological processes, human reproduction varies in significant ways from that of common laboratory animals like mice or fruit flies. Furthermore, many key steps, like the development and migration of primordial germ cells to the gonads, happen within days or weeks of conception. These challenges have made the process difficult to study.

Reijo Pera, who is now a professor of cell biology and neurosciences at Montana State University, is the senior author of a paper describing the research, which will be published May 1 in Cell Reports. The experiments in the study were conducted at Stanford, and Stanford postdoctoral scholar Cyril Ramathal, PhD, is the lead author of the paper.

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

Excerpt from:
Stem cells from some infertile men form germ cells when transplanted into mice, study finds

Stem cells made from the skin of adult, infertile men yield primordial germ cells -- cells that normally become sperm -- when transplanted into the reproductive system of mice, according to researchers at the Stanford University School of Medicine and Montana State University.

The infertile men in the study each had a type of genetic mutation that prevented them from making mature sperm -- a condition called azoospermia. The research suggests that the men with azoospermia may have had germ cells at some point in their early lives, but lost them as they matured to adulthood.

Although the researchers were able to create primordial germ cells from the infertile men, their stem cells made far fewer of these sperm progenitors than did stem cells from men without the mutations. The research provides a useful, much-needed model to study the earliest steps of human reproduction.

"We saw better germ-cell differentiation in this transplantation model than we've ever seen," said Renee Reijo Pera, PhD, former director of Stanford's Center for Human Embryonic Stem Cell Research and Education. "We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages."

A difficult process to study

Unlike many other cellular and physiological processes, human reproduction varies in significant ways from that of common laboratory animals like mice or fruit flies. Furthermore, many key steps, like the development and migration of primordial germ cells to the gonads, happen within days or weeks of conception. These challenges have made the process difficult to study.

Reijo Pera, who is now a professor of cell biology and neurosciences at Montana State University, is the senior author of a paper describing the research, published May 1 in Cell Reports. The experiments in the study were conducted at Stanford, and Stanford postdoctoral scholar Cyril Ramathal, PhD, is the lead author of the paper.

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

The germ cells made from stem cells stopped differentiating in the mice before they produced mature sperm (likely because of the significant differences between the reproductive processes of humans and mice) regardless of the fertility status of the men from whom they were derived. However, the fact that the infertile men's cells could give rise to germ cells at all was a surprise.

Previous research in mice with a similar type of infertility found that although they had germ cells as newborns, these germ cells were quickly depleted. The Stanford findings suggests that the infertile men may have had at least a few functioning germ cells as newborns or infants. Although more research needs to be done, collecting and freezing some of this tissue from young boys known to have this type of infertility mutation may give them the option to have their own children later in life, the researchers said.

The rest is here:
Stem cells from some infertile men form germ cells when transplanted into mice

Topics: editors picks, family, relationships, science, sex

INFERTILE men could in future be offered a new form of treatment based on converting their skin cells into the sperm-making tissue that is missing in their testicles, scientists have said.

A study has found that it is possible to convert skin cells into male "germ cells" which are responsible for sperm production, using an established technique for creating embryonic-like stem cells, in a form of genetic engineering.

The research, published in the journal Cell Reports, showed that stem cells derived from human skin become active germ cells when transplanted into the testes of mice - even when the man suffers from a genetic condition where he lacks functioning germ cells in his own testes.

Although the mice had functioning human male germ cells, they did not produce human sperm, said Renee Reijo Pera, of Montana State University, who led the study.

"There is an evolutionary block that means that when germ cells from one species are transferred to another, there is not full spermatogenesis unless the species are very closely related," she added.

Read more from the original source:
Skin cells provide new hope for infertile men

PUBLIC RELEASE DATE:

1-May-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Researchers reporting in the Cell Press journal Cell Reports on May 1st have successfully coaxed stem cells made from the skin cells of infertile men into producing sperm cell precursors. These induced pluripotent stem cells (iPSCs) produced sperm precursors following transplantation into the testes of mice.

The findings help to explain a genetic cause of male infertility and offer a window into basic sperm biology. The approach also holds considerable potential for clinical application, the researchers say.

"Our results are the first to offer an experimental model to study sperm development," said Renee Reijo Pera of the Institute for Stem Cell Biology & Regenerative Medicine and Montana State University. "Therefore, there is potential for applications to cell-based therapies in the clinic, for example, for the generation of higher quality and numbers of sperm in a dish.

"It might even be possible to transplant stem-cell-derived germ cells directly into the testes of men with problems producing sperm," she added. However, getting to that point will require considerable study to ensure the safety and practicality.

Infertility affects 10% to 15% of couples. Moreover, as the researchers note, genetic causes of infertility are surprisingly prevalent among men, most commonly due to the spontaneous loss of key genes on the Y sex chromosome. But the causes at the molecular level have not been well understood.

Reijo Pera said her primary motivation is to understand the fundamental decision early in development that enables the production of sperm cell precursors and ultimately sperm. One way to do that is to study cells lacking genes that are required for sperm production.

The researchers looked to infertile but otherwise normal men with deletions encompassing three Y chromosome azoospermia factor (AZF) regions, which are associated with the production of few or no sperm. They found that iPSCs derived from AZF-deleted cells were compromised in their ability to form sperm in a dish. But when those cells were transplanted into the seminiferous tubules of mice, they produced germ-cell-like cells (though significantly fewer than iPSCs derived from people without the AZF deletion do).

Read the original here:
Sperm precursors made from stem cells of infertile men

Malaysia to open new budget airport in MH370 shadow

Sepang (Malaysia) (AFP) - Malaysia this week opens what it calls the world's largest airport built specifically for low-cost airlines, a project driven by budget travel's phenomenal growth but which debuts under the shadow of missing flight MH370. The $1.2 billion facility near the main Kuala Lumpur International Airport (KLIA) was originally targeted to open three years ago but has been hit by repeated delays, amid concerns over safety and subpar construction, even as costs have doubled. But the new KLIA2 budget terminal will begin operations Friday with an initial 56 flights, increasing the load as airlines move full operations over from a nearby existing facility in coming days. Its modern design features soaring ceilings, natural lighting, people-mover belts and improved connectivity with access to an existing express airport train to Kuala Lumpur 50 kilometres (31 miles) away.

Read the rest here:
Stem Cells Made Using Human Cloning Technique 'Hold Potential Cure for Diabetes'

SAN FRANCISCO, April 28 (UPI) -- An international team of researchers developed skin grown from human stem cells that may eliminate using animals for drug and cosmetics testing and help develop news therapies for skin disorders.

The team led by Kings College London and the San Francisco Veteran Affairs Medical Center developed the first laboratory-grown epidermis -- the outer layer of skin -- similar to real skin.

"The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skins barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis, (eczema)," Dr. Theodora Mauro, leader of the San Francisco Veteran Affairs Medical Center team, said in a statement.

"We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

The new skin is grown from human pluripotent stem cells -- stem cells that have the potential to differentiate into almost any cell in the body. Under the right circumstances, the stem cell can produce almost all of the cells in the body.

The human induced pluripotent stem cells can produce an unlimited supply of pure keratinocytes, the predominant cell type in the outermost layer of skin that closely match keratinocytes generated from human embryonic stem cells.

The artificial skin forms a protective barrier between the body and the environment keeping out microbes and toxins, while not allowing water from escaping the body.

The findings were published in the journal Stem Cell Reports.

More:
Researchers create artificial skin using stem cells

Scientists have used cloning technology to make stem cells from a woman with Type 1 diabetes that are genetically matched to her and to her disease.

They hope to someday use such cells as tailor-made transplants to treat or potentially even cure the disease, which affects millions and which now has few treatment options other than careful diet and regular use of insulin.

Its the second report his month of success in using cloning technology to make human embryonic stem cells the cells that eventually create a complete human being and that scientists hope to harness to treat diseases ranging from diabetes to Parkinsons and injuries that cause paralysis or organ damage.

I think this is going to become reality, Dr. Dieter Egli of the New York Stem Cell Foundation, whose report is published in the journal Nature on Monday, told reporters. It may be a bit in the future but it is going to happen.

The technique they use is called somatic cell nuclear transfer the same method used to make Dolly, the sheep who was the first mammal to be cloned, in 1996. Scientists remove the nucleus from a normal cell, clear the nucleus from a human egg cell, then inject the nucleus from the skin cell into the egg.

I think this is going to become reality."

Various chemical or electrical tricks can be used to start the egg growing as if it had been fertilized by sperm. In this case, they used DNA from a woman with Type 1 diabetes, and they said they used an improved method to trick the egg into developing.

It got to whats called a blastocyst a ball of cells that has not yet begun to differentiate into the different types of cells and tissues in the body, such as nerve cells, blood cells and bone cells. They removed individual cells and used various chemical baths to direct them to form into the desired cell type the beta cells in the pancreas that make insulin and that are destroyed in diabetes. These cells carry the patients own unique DNA, including whatever genetic mistakes led to her diabetes.

These stem cells could therefore be used to generate cells for therapeutic cell replacement, they wrote in their report.

Scientists have cloned sheep, pigs, mice and monkeys, but its been far harder to clone human beings. Its partly because of the controversy few people advocate cloning humans for the purpose of making babies, and many people object to destroying a human embryo, even one that only ever existed in a lab dish.

Continued here:
Stem Cells Made From Cloning Diabetic Woman

Researchers hope stem cells could one day treat chronic conditions like diabetes and Parkinsons disease.

Healthy bloom: Insulin, shown in red, is being produced by cells that started as embryonic stem cells derived from a patient with type 1 diabetes.

A series of breakthroughs in cloning technology over the last year and a half are stoking hopes that cells could be used as treatments for patients with chronic, debilitating diseases such as diabetes and Parkinsons.

In January 2013, researchers at the Oregon Health and Science University reported that they had successfully created embryonic stem cells from a human embryo formed when the nucleus of one persons cell was transferred into another persons egg that had its original nucleus removed (see Human Embryonic Stem Cells Cloned). That was the first time stem cells had been made from such a cloned embryo, and the advance provides a potential route by which scientists could create various kinds of replacement cells based on a patients own genome. Many other research teams are pursuing another method of creating stem cells from a patients own cells, but some believe cells made with the cloning technique could be more likely to develop into a wide variety of cell types.

In the most recent advance for the cloning-based approach, a new report describes stem cells produced by cloning a skin cell from a woman with type 1 diabetes. The researchers were then able to turn those stem cells into insulin-producing cells resembling the beta cells that are lost in that disease. The immune system attacks these pancreatic cells, leaving patients unable to properly regulate their blood sugar levels.

Susan Solomon, a coauthor of the new study and cofounder of the New York Stem Cell Foundation (NYSCF), told reporters the results are an important step forward in our quest to develop healthy patient-specific stem cells to be used to replace cells that are diseased or dead.

The ultimate idea is to treat diabetes with insulin-producing cells made from a patients own cells and a donated egg. Currently, insulin-producing cells harvested from a cadaver are transplanted into some diabetes patients. But patients treated this way must take immunosuppressing drugs, and the number of cadaver cells is limited.

The cloned cells are thought to be better accepted by the immune system. But given that the body attacks its own beta cells, how can researchers prevent the immune destruction of the transplants? Its very difficult, says Solomon. We are acutely aware of the need to address both sides of the problem.

There are also regulatory issues surrounding the cloning method. Lead researcher and coauthor Dieter Egli began the research at Harvard University but moved it to the New York institution because Massachusetts restrictions on egg donation prevented the work from progressing.

Egg supply is another challenge. The cloning works about 10 percent of the time, and only three of the four cloned embryos in the experiment led to viable stem-cell lines. When you think about wider application of this technology for patients with diabetes, cardiovascular disease, [and others], you are talking about hundreds of millions of people, says Robert Lanza, a stem-cell pioneer at Advanced Cell Technology and coauthor of a recent cloning report. When you start talking about numbers like that, its just not going to be practical to use these cells in that patient-specific way.

See the rest here:
Stem Cells from a Diabetes Patient

Scientists have used cloning technology to make stem cells from a woman with Type 1 diabetes that are genetically matched to her and to her disease.

They hope to someday use such cells as tailor-made transplants to treat or potentially even cure the disease, which affects millions and which now has few treatment options other than careful diet and regular use of insulin.

Its the second report his month of success in using cloning technology to make human embryonic stem cells the cells that eventually create a complete human being and that scientists hope to harness to treat diseases ranging from diabetes to Parkinsons and injuries that cause paralysis or organ damage.

I think this is going to become reality, Dr. Dieter Egli of the New York Stem Cell Foundation, whose report is published in the journal Nature on Monday, told reporters. It may be a bit in the future but it is going to happen.

The technique they use is called somatic cell nuclear transfer the same method used to make Dolly, the sheep who was the first mammal to be cloned, in 1996. Scientists remove the nucleus from a normal cell, clear the nucleus from a human egg cell, then inject the nucleus from the skin cell into the egg.

I think this is going to become reality."

Various chemical or electrical tricks can be used to start the egg growing as if it had been fertilized by sperm. In this case, they used DNA from a woman with Type 1 diabetes, and they said they used an improved method to trick the egg into developing.

It got to whats called a blastocyst a ball of cells that has not yet begun to differentiate into the different types of cells and tissues in the body, such as nerve cells, blood cells and bone cells. They removed individual cells and used various chemical baths to direct them to form into the desired cell type the beta cells in the pancreas that make insulin and that are destroyed in diabetes. These cells carry the patients own unique DNA, including whatever genetic mistakes led to her diabetes.

These stem cells could therefore be used to generate cells for therapeutic cell replacement, they wrote in their report.

Scientists have cloned sheep, pigs, mice and monkeys, but its been far harder to clone human beings. Its partly because of the controversy few people advocate cloning humans for the purpose of making babies, and many people object to destroying a human embryo, even one that only ever existed in a lab dish.

See the rest here:
Diabetic Woman's Cells Are Turned Into Embryonic Stem Cells

Scientists have taken skin cells from a woman suffering from type 1 diabetes, reprogrammed them into embryonic stem cells, and then converted those cells into insulin-producing cells in mice, according to a new study.

The announcement, which comes soon after another stem cell success involving therapeutic cloning, was published Monday in the journal Nature.

"This advance brings us a significant step closer to the development of cell replacement therapies," said senior study author Dieter Egli, a researcher at the New York Stem Cell Foundation.

Embryonic stem cells, or pluripotent cells, are cells that can reproduce endlessly and transform themselves into any type of human tissue. Researchers hope that the cells will one day be used to create transplant tissues that will not be rejected by the patient's body, because they carry their own DNA.

Egli and his colleagues used a cloning technique known as somatic cell nuclear transfer, or SCNT -- a process similar to the one used to clone "Dolly" the sheep in 1996.

The process involves removing the nucleus from a human egg cell, replacing it with the nucleus from a foreign "donor" cell, and then allowing the egg to divide and develop for a period of days. The developing embryo will contain a mass of pluripotent cells, which are removed and used to create a line of reproducing cells.

If the cloned embryo were implanted in the womb of a surrogate mother -- an act scientists consider unethical for a number of reasons -- it could possibly develop into a baby.

Up until now, the stem cell field has relied on a very different method of pluripotent cell production called induced pluripotency. The process is viewed as being much easier than SCNT, because it does not involve the controversial use of human egg cells, which are also difficult to obtain.

At a news conference, Egli told reporters that the SCNT process was becoming increasingly refined and should be viewed as a reliable source of pluripotent cells.

"For me this is the way to go," Egli said. "This is about reprogramming a patient's own cells, with their own genotype, with their own DNA that are immunologically matched to them and no one else, essentially. I think this is going to become a reality."

Read the original post:
Scientists report another embryonic cloning success

Skin grown in the laboratory can replace animals in drug and cosmetics testing, UK scientists say.

A team led by King's College London has grown a layer of human skin from stem cells - the master cells of the body.

Stem cells have been turned into skin before, but the researchers say this is more like real skin as it has a permeable barrier.

It offers a cost-effective alternative to testing drugs and cosmetics on animals, they say.

The outermost layer of human skin, known as the epidermis, provides a protective barrier that stops moisture escaping and microbes entering.

Scientists have been able to grow epidermis from human skin cells removed by biopsy for several years, but the latest research goes a step further.

The research used reprogrammed skin cells - which offer a way to produce an unlimited supply of the main type of skin cell found in the epidermis.

They also grew the skin cells in a low humidity environment, which gave them a barrier similar to that of true skin.

Skin barrier

Lead researcher Dr Dusko Ilic, of King's College London, told BBC News: "This is a new and suitable model that can be used for testing new drugs and cosmetics and can replace animal models.

More here:
Human Skin Grown In Lab 'Can Replace Animal Testing'

A team of researchers from Kings College London and the San Francisco Veteran Medical Center announced on Thursday that they were able to grow an epidermis that had the same permeability as real human skin, by using pluripotent stem cells. Pluripotent stem cells are cultured from adult cells and can develop into any type of cell or tissue.

Researchers say the artificial human skin offers a cost-effective alternative technique for testing drugs and cosmetics.

Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics, Dusko Ilic, leader of the team at King's College London, said in a statement. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery.

The new study, published in the journalStem Cell Reports,details how researchers triggered pluripotent stem cells to generate an unlimited supply of pure keratinocytes -- the primary cell type of the epidermis. In a high-humidity environment, scientists grew three-dimensional epidermal samples.

The samples engineered in the lab showed no significant differences in structure or function compared with real human skin samples, according to researchers.

Since the 1920s, the U.S. and other industrialized nations have used animals to test the safety and effectiveness of various drugs and vaccines. In the cosmetic industry, nonhuman test subjects, including rabbits, monkeys, rats and dogs, undergo skin and eye irritation tests in which chemicals are rubbed onto sections of shaved skin or dripped into the eyes of restrained test subjects. Some are even forced to swallow large amounts of certain chemicals to determine what constitutes a lethal dose.

While the use of animal testing, particularly Draize Testing, in which test substances are administered to the eye or skin has declined in recent years in the U.S. and Europe, it is still legal in 80 percent of countries. According to the Humane Society, in China alone, an estimated 300,000 animal die each year in cosmetic tests.

Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, Ilic said. [They can] be tailored to study a range of skin conditions and sensitivities in different populations.

Read the rest here:
First Human Skin Sample 'Grown' In Lab, Could Artificial Epidermis End Animal Testing?