Archive for the ‘Cell Medicine’ Category
Welcome to the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, one of the largest and most comprehensive programs of its kind in the United States.
In some 125 labs, scientists are carrying out studies, in cell culture and animals, aimed at understanding and developing treatment strategies for such conditions as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinsons disease, Lou Gehrigs disease, spinal cord injury and cancer.
While the scientific foundation for the field is still being laid, UCSF scientists are beginning to move their work toward human clinical trials. A team of pediatric specialists and neurosurgeons is carrying out the second brain stem cell clinical trial ever conducted in the United States, focusing on a rare disease, inherited in boys, known as Pelizaeus-Merzbacher disease.
Others are working to develop strategies for treating diabetes, brain tumors, liver disease and epilepsy. The approach for treating epilepsy potentially also could be used to treat Parkinsons disease, as well as the pain and spasticity that follow brain and spinal cord injury.
The center is structured along seven research pipelines aimed at driving discoveries from the lab bench to the patient. Each pipeline focuses on a different organ system, including the blood, pancreas, liver, heart, reproductive organs, nervous system, musculoskeletal tissues and skin. And each of these pipelines is overseen by two leaders of international standing one representing the basic sciences and one representing clinical research. This approach has proven successful in the private sector for driving the development of new therapies.
The center, like all of UCSF, fosters a highly collaborative culture, encouraging a cross-pollination of ideas among scientists of different disciplines and years of experience. Researchers studying pancreatic beta cells damaged in diabetes collaborate with those who study nervous system diseases because stem cells undergo similar molecular signaling on the way to becoming both cell types. The opportunity to work in this culture has drawn some of the countrys premier young scientists to the center.
While the focus of the science is the future, UCSFs history in the field dates back to 1981, when Gail Martin, PhD, co-discovered embryonic stem cells in mice and coined the term embryonic stem cell. Two decades later, UCSFs Roger Pedersen, PhD, developed two of the first human embryonic stem cell lines, following the groundbreaking discovery by University of Wisconsins James Thomson, PhD, of a way to derive the cells.
Today, the Universitys faculty includes Shinya Yamanaka, MD, PhD, of the UCSF-affiliated J. David Gladstone Institutes and Kyoto University. His discovery in 2006 of a way to reprogram ordinary skin cells back to an embryonic-like state has given hope that someday these cells might be used in regenerative medicine.
Yamanakas seminal finding highlights the unexpected and dramatic discoveries that can characterize scientific research. In labs throughout UCSF and beyond, the goal is to move such findings into patients.
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Eli and Edythe Broad Center of Regeneration Medicine and …
Home Molecular & Cellular Medicine Menu
Research in the Molecular and Cellular Medicine department spans a wide range of biological processes, from structure and function of biomolecules to cell physiology. Emphasis is placed on understanding normal and abnormal biological function at the molecular and cellular levels. Using state-of-the-art biophysical technologies, research programs at the molecular level focus on understanding how proteins are synthesized, folded, assembled into functional macromolecules and trafficked throughout the cell. Reverse genetic approaches are used to elucidate the roles of newly discovered proteins and define functional protein domains. Research programs that bridge molecular and cellular levels focus on understanding mechanisms of basic cellular physiology (DNA replication, transcription, translation and protein sorting), molecules that control complex regulatory pathways (signal transduction, gene regulation, epigenetics, development and differentiation) and the molecular basis for cancer. Many faculty members have strong collaborative ties with Texas A&M University research groups in the Chemistry and Biochemistry/Biophysics departments or belong to multi-disciplinary research groups affiliated with Texas A&M University, including programs in Genetics, Neurosciences and Virology.
440 Reynolds Medical Building College Station, TX 77843-1114 Phone: (979) 436-0856 Fax: (979) 847-9481 Toll Free: (800) 298-2260 (U.S. only)
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Molecular & Cellular Medicine
Bone marrow transplant offers the only potential cure for sickle cell anemia. But finding a donor is difficult and the procedure has serious risks associated with it, including death.
As a result, treatment for sickle cell anemia is usually aimed at avoiding crises, relieving symptoms and preventing complications. If you have sickle cell anemia, you’ll need to make regular visits to your doctor to check your red blood cell count and monitor your health. Treatments may include medications to reduce pain and prevent complications, blood transfusions and supplemental oxygen, as well as a bone marrow transplant.
Medications used to treat sickle cell anemia include:
Hydroxyurea (Droxia, Hydrea). When taken daily, hydroxyurea reduces the frequency of painful crises and may reduce the need for blood transfusions. Hydroxyurea seems to work by stimulating production of fetal hemoglobin a type of hemoglobin found in newborns that helps prevent the formation of sickle cells. Hydroxyurea increases your risk of infections, and there is some concern that long-term use of this drug may cause tumors or leukemia in certain people. However, this hasn’t yet been seen in studies of the drug.
Hydroxyurea was initially used just for adults with severe sickle cell anemia. Studies on children have shown that the drug may prevent some of the serious complications associated with sickle cell anemia. But the long-term effects of the drug on children are still unknown. Your doctor can help you determine if this drug may be beneficial for you or your child.
Using a special ultrasound machine (transcranial), doctors can learn which children have a higher risk of stroke. This test can be used on children as young as 2 years, and those who are found to have a high risk of stroke are then treated with regular blood transfusions.
Childhood vaccinations are important for preventing disease in all children. But, these vaccinations are even more important for children with sickle cell anemia, because infections can be severe in children with sickle cell anemia. Your doctor will make sure your child receives all of the recommended childhood vaccinations. Vaccinations, such as the pneumococcal vaccine and the annual flu shot, are also important for adults with sickle cell anemia.
In a red blood cell transfusion, red blood cells are removed from a supply of donated blood. These donated cells are then given intravenously to a person with sickle cell anemia.
Blood transfusions increase the number of normal red blood cells in circulation, helping to relieve anemia. In children with sickle cell anemia at high risk of stroke, regular blood transfusions can decrease their risk of stroke.
Blood transfusions carry some risk. Blood contains iron. Regular blood transfusions cause an excess amount of iron to build up in your body. Because excess iron can damage your heart, liver and other organs, people who undergo regular transfusions may need treatment to reduce iron levels. Deferasirox (Exjade) is an oral medication that can reduce excess iron levels.
Breathing supplemental oxygen through a breathing mask adds oxygen to your blood and helps you breathe easier. It may be helpful if you have acute chest syndrome or a sickle cell crisis.
A stem cell transplant, also called a bone marrow transplant, involves replacing bone marrow affected by sickle cell anemia with healthy bone marrow from a donor. Because of the risks associated with a stem cell transplant, the procedure is recommended only for people who have significant symptoms and problems from sickle cell anemia.
If a donor is found, the diseased bone marrow in the person with sickle cell anemia is first depleted with radiation or chemotherapy. Healthy stem cells from the donor are filtered from the blood. The healthy stem cells are injected intravenously into the bloodstream of the person with sickle cell anemia, where they migrate to the bone marrow cavities and begin generating new blood cells. The procedure requires a lengthy hospital stay. After the transplant, you’ll receive drugs to help prevent rejection of the donated stem cells.
A stem cell transplant carries risks. There’s a chance that your body may reject the transplant, leading to life-threatening complications. In addition, not everyone is a candidate for transplantation or can find a suitable donor.
Doctors treat most complications of sickle cell anemia as they occur. Treatment may include antibiotics, vitamins, blood transfusions, pain-relieving medicines, other medications and possibly surgery, such as to correct vision problems or to remove a damaged spleen.
Scientists are studying new treatments for sickle cell anemia, including:
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Sickle cell anemia Treatments and drugs – Mayo Clinic
From the United States Senate to houses of worship, and even to the satirical television show “South Park,” stem cells have been in the spotlight — though not always in the kindest light. Since early research has focused on the use of embryonic stem cells (cells less than a week old), the very act of extracting these cells has raised a raft of ethical questions for researchers and the medical community at large, with federal funding often hanging in the balance.
However, the advances in stem cell research and the subsequent applications to modern medicine can’t be ignored. According to the National Institutes of Health (NIH), stem cells are being considered for a wide variety of medical procedures, ranging from cancer treatment to heart disease and cell-based therapies for tissue replacement.
Why? To answer that question, you have to understand what stem cells are. Called “master” cells or “a sort of internal repair system,” these remarkable-yet-unspecialized cells are able to divide, seemingly without limits, to help mend or replenish other living cells [sources: Mayo Clinic; NIH]. In short, these cells are the cellular foundation of the entire human body, or literally the body’s building blocks.
By studying these cells and how they develop, researchers are closing in on a better understanding of how our bodies grow and mature, and how diseases and other abnormalities take root. The research work that began with mouse embryos in the early 1980s eventually helped scientists devise a way to isolate stem cells from human embryos by the late 1990s.
Embryonic, or pluripotent, stem cells are taken from human embryos that are less than a week old. These cells are wildly versatile, capable of dividing into more stem cells or becoming any type of cell in the human body (roughly 220 types, including muscle, nerve, blood, bone and skin). Researchers have also recently found stem cells in amniotic fluid taken from pregnant women during amniocentesis, a fairly routine procedure used to determine potential complications, such as Down syndrome.
However, recent research has indicated that adult stem cells, once thought to be more limited in their capabilities, are actually much more versatile than originally believed. Though not as “pure” as embryonic stem cells, due to environmental conditions that exist in the real world — ranging from air pollution to food impurities — adult stem cells are nonetheless garnering attention, if only because they don’t incite the same ethical debate as embryonic stem cells.
So, what are the cutting-edge uses for stem cells?
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How are stem cells used in medicine today? – HowStuffWorks
Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, open access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in todays scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering bench to bedside research into clinical strategies.
Oxidative Medicine and Cellular Longevity was founded in 2008 by Professor Kenneth Maiese who served as the Editor-in-Chief of the journal between 2008 and 2011.
The most recent Impact Factor for Oxidative Medicine and Cellular Longevity is 3.516 according to 2014 Journal Citation Reports released by Thomson Reuters in 2015.
Oxidative Medicine and Cellular Longevity currently has an acceptance rate of 42%. The average time between submission and final decision is 53 days and the average time between acceptance and publication is 28 days.
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Oxidative Medicine and Cellular Longevity An Open Access …
Message from the Chair
Welcome to the Department of Regenerative Medicine and Cell Biology. The goal of the department is to apply our knowledge of molecular and cellular biology to understand and reverse human disease. Regenerative medicine is an emerging field that aims to revolutionize the treatment of disease by providing cures rather than treating symptoms. It relies on multidisciplinary approaches that require expertise in diverse areas. Approaches include the use of stem cells to provide limitless supplies of cells for transplant therapy and disease modeling, bioengineering and tissue engineering to generate replacement tissues and organs, and the production of transgenic animals to study the fundamental molecular basis of organ formation and disease. The department has active research programs in tissue fabrication and bioengineering, developmental biology, cardiovascular and liver disease, cancer biology, cell signaling, and drug development. The Department is also heavily involved in biomedical education through the training of medical and graduate students. Regenerative medicine is at a particularly exciting stage, with investigators being poised to make discipline-changing advances of high impact. The field is on the cusp of revolutionizing biomedical science, and as regenerative medicine researchers we are limited only by our imaginations.
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Department of Regenerative Medicine and Cell Biology
Sickle cell anemia is a disease in which your body produces abnormally shaped red blood cells. The cells are shaped like a crescent or sickle. They don’t last as long as normal, round red blood cells. This leads to anemia. The sickle cells also get stuck in blood vessels, blocking blood flow. This can cause pain and organ damage.
A genetic problem causes sickle cell anemia. People with the disease are born with two sickle cell genes, one from each parent. If you only have one sickle cell gene, it’s called sickle cell trait. About 1 in 12 African Americans has sickle cell trait.
The most common symptoms are pain and problems from anemia. Anemia can make you feel tired or weak. In addition, you might have shortness of breath, dizziness, headaches, or coldness in the hands and feet.
A blood test can show if you have the trait or anemia. Most states test newborn babies as part of their newborn screening programs.
Sickle cell anemia has no widely available cure. Treatments can help relieve symptoms and lessen complications. Researchers are investigating new treatments such as blood and marrow stem cell transplants, gene therapy, and new medicines.
NIH: National Heart, Lung, and Blood Institute
Personalized Regenerative Medicine
Making sure the bases are covered. That is how Dr David Steenblock and Personalized Regenerative Medicine delivers on its mission is to provide advanced care for chronic and degenerative disease. Our first step is to do a complete physical evaluation, including all appropriate lab work to help us determine what are the issues that each View Article
When a doctor sees a patient for the first time he will ask for copies of medical records as part of gathering information and data that, in combination with taking a medical history and doing relevant exams and tests, helps him arrive at a diagnosis (or confirm previously made ones) and formulate a medical care View Article
Providing advanced care for chronic and degenerative disease often times requires augmenting natures own repair & restoration mechanism with stem cells. This is one way that Dr David Steenblock and Personalized Regenerative Medicine provide comprehensive care it our patients. When diseasesets in and begins to progress the sufferers bodytries to repair the damage by activating View Article
In his decades of private practice, Dr David Steenblock and Personalized Regenerative Medicine has established himself as a pioneer in many fields of medicine. Dr David Steenblock and Personalized Regenerative Medicines mission is to deliver advanced care for chronic and degenerative diseases such as ALS, Stroke, Cerebral Palsy and Cardiac conditions. From stroke care andacute View Article
Putting it all together. This where Dr David Steenblock and Personalized Regenerative Medicine separate themselves from their peers in delivering advanced care for chronic and degenerative disease. Once a patients diagnosis is confirmed, modified or even overturned and the results of all tests ordered are in, Dr. Steenblock formulates a treatment plan. The therapeutic regimen View Article
Researchers in the USA have offered an explanation for the sparse inflammatory responses seen in some fungal infections.This may help physicians netter understand how to treat certain chronic and degenerative diseases, such as ALS. Stephen Klotz at the University of Arizona and co-workers examined autopsy specimens from 15 patients with histological evidence of aspergillosis, mucormycosis, View Article
Supercharged Chelation therapy is now available. If you already have read about or experienced the benefits of chelation but wondering if there was some way to enhance the therapy Dr Steenblock has come up with a better method for re-vitalization of your arteries and your entire body. The secret is STEM CELLS! The most simple View Article
While the promise of stem cell medicine has never been greater, the question of outcomes has long been an issue. Until now. Dr Steenblock has been focused on two critical issues in his career: identifying the causes of disease and treating patients. Over his many years of practice, Dr Steenblock has treated tens of thousands View Article
Dr Steenblock has long believed that Alzheimers Disease is connected to bacteria that enters the nervous system due to trauma. Recent articles have come to show that his ideas and research are correct. Traces of fungus have been discovered in the brains of Alzheimers sufferers, researchers said Thursday, relaunching the question: might the disease be View Article
Chelation therapy, an alternative technique long dismissed by conventional heart doctors, has taken a giant step toward becoming a first-line mainstream medical treatment, thanks to a boost from the National Institutes of Health. Dr Steenblock has been utilizing this powerful therapeutic approach for many years to treat various conditions. The federal health agencys National Center View Article
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Personalized RegenerativeMedicine : Dr David Steenblock
Adult (Somatic) stem cells are unspecialized cells that are found in different parts of the body and, depending on the source tissue, have different properties. Adult stem cells are capable of self-renewal and give rise to daughter cells that are specialized to form the cell types found in the original body part.
Adult stem cells are multipotent, meaning that they appear to be limited in the cell types that they can produce based on current evidence. However, recent scientific studies suggest that adult stem cells may have more plasticity than originally thought. Stem cell plasticity is the ability of a stem cell from one tissue to generate the specialized cell type(s) of another tissue. For example, bone marrow stromal cells are known to give rise to bone cells, cartilage cells, fat cells and other types of connective tissue (which is expected), but they may also differentiate into cardiac muscle cells and skeletal muscle cells (this was not initially thought possible).
Hematopoietic stem cells that give rise to all blood and immune cells are today the most understood of the adult stem cells. Hematopoietic stem cells from bone marrow have been providing lifesaving cures for leukemia and other blood disorders for over 40 years. Hematopoietic stem cells are primarily found in the bone marrow but have also been found in the peripheral blood in very low numbers. Compared to adult stem cells from other tissues, hematopoietic stem cells are relatively easy to obtain.
Mesenchymal stem cells are also found in the bone marrow. Mesenchymal stem cells are a mixed population of cells that can form fat cells, bone, cartilage and ligaments, muscle cells, skin cells and nerve cells.
Hematopoietic and stromal stem cell differentiation:4
Umbilical cord blood from newborns is a rich source of hematopoietic stem cells. Research has found that these stem cells are less mature than other adult stem cells, meaning that they are able to proliferate longer in culture and may contribute to a broader range of tissues. Research is ongoing to determine whether umbilical cord stem cells are pluripotent or multipotent and the extent of their plasticity.
Cord blood, which traditionally has been discarded, has emerged as an alternative source of hematopoietic stem cells for the treatment of leukemia, lymphoma and other lethal blood disorders. It has also been used as a life-saving treatment for children with infantile Krabbes disease, a lysosomal storage disease that produces progressive neurological deterioration and death in early childhood.
Regardless of the adult stem cells’ source bone marrow, umbilical cord blood or other tissues these cells are present in minute quantities. This makes identification, isolation and purification challenging. Scientists are currently trying to determine how many kinds of adult stem cells exist and where they are located in the body.
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Cell Therapy and Regenerative Medicine
Stem cells have the potential to treat a wide range of diseases. Here, discover why these cells are such a powerful tool for treating diseaseand what hurdles experts face before new therapies reach patients.
How can stem cells treat disease? What diseases could be treated by stem cell research? How can I learn more about CIRM-funded research in a particular disease? What cell therapies are available right now? When will therapies based on embryonic stem cells become available? What about the therapies that are available overseas? Why does it take so long to create new therapies? How do scientists get stem cells to specialize into different cell types? How do scientists test stem cell therapies? Can’t stem cell therapies increase the chances of a tumor? Is there a risk of immune rejection with stem cells? How do scientists grow stem cells in the right conditions?
When most people think about about stem cells treating disease they think of a stem cell transplant.
In a stem cell transplant, embryonic stem cells are first specialized into the necessary adult cell type. Then, those mature cells replace tissue that is damaged by disease or injury. This type of treatment could be used to:
But embryonic stem cell-based therapies can do much more.
Any of these would have a significant impact on human health without transplanting a single cell.
In theory, theres no limit to the types of diseases that could be treated with stem cell research. Given that researchers may be able to study all cell types via embryonic stem cells, they have the potential to make breakthroughs in any disease.
CIRM has created disease pages for many of the major diseases being targeted by stem cell scientists. You can find those disease pages here.
You can also sort our complete list of CIRM awards to see what we’ve funded in different disease areas.
Many clinical trials for embryonic stem cell-based therapies have begun in recent months. Results from those won’t be available until the trials reveal that the therapies are safe and effectivewhich could take a few years.
The only stem cell-based therapy currently in use is in bone marrow transplantation. Blood-forming stem cells in the bone marrow were the first stem cells to be identified and were the first to be used in the clinic. This life-saving technique has helped thousands people worldwide who had been suffering from blood cancers, such as leukemia.
In addition to their current use in cancer treatments, research suggests that bone marrow transplants will be useful in treating autoimmune diseases and in helping people tolerate transplanted organs.
Other therapies based on adult stem cells are currently in clinical trials. Until those trials are complete we won’t know which type of stem cell is most effective in treating different diseases.
There is no way to predict when the first human embryonic stem cell therapies will become widely available. Several applications with the FDA to begin human trials of embryonic stem cell-based therapies have been approved. In general, the path from the first human trial to widespread use is on the order of a decade. That long time frame is a result of the many steps a therapy must go through in order to show that it is both safe and effective. Only once those steps are complete will the FDA approve the therapy for general use.
If embryonic stem cells follow a normal path it could still be many years before therapies based on embryonic stem cells are widely available. However, if researchers gave up on therapies simply because the path towards FDA approval is long, we would not have any of the lifesaving technologies that are now commonplace: recombinant insulin, bone marrow transplantation or chemotherapy drugs.
Find Out More: Read the top ten things to know about stem cell treatments (from ISSCR) Alan Lewis talks about getting an embryonic stem cell-based therapy to patients (3:46)
Many overseas clinics advertise miraculous stem cell therapies for a wide range of incurable diseases. This phenomenon is called stem cell tourism and is currently a source of concern for reputable stem cell scientists. International (and even domestic) clinics are offering up therapies that have not been tested for safety or even for effectiveness. In the past few years, some patients who visited those clinics have died as a result of receiving unproven, untested stem cells.
Find Out More: Learn more about the issue on our StemCell Tourism page. Jeanne Loring discusses concerns about stem cell tourism (3:38) CIRM/ISSCR panel on stem cell tourism
Embryonic stem cells hold the potential to treat a wide range of diseases. However, the path from the lab to the clinic is a long one. Before testing those cells in a human disease, researchers must grow the right cell type, find a way to test those cells, and make sure the cells are safe in animals before moving to human trials.
Find Out More: Hans Keirstead talks about hurdles in developing a new therapy (5:07)
One of the biggest hurdles in any embryonic stem cell-based therapy is coaxing stem cell to become a single the cell type. The vital process of maturing stem cells from a pluripotent state to an adult tissue type is called differentiation.
Guiding embryonic stem cells to become a particular cell type has been fraught with difficulty. Normally, stem cells growing in a developing embryo receive a carefully choreographed series of signals from the surrounding tissue. In a lab dish, researchers have to mimic those signals. Add the signals in the wrong order or the wrong dose and the developing cells may choose to remain immatureor become the wrong cell type
Many decades of research has uncovered many of the signals needed to properly differentiate cells. Other signals are still unknown. Many CIRM-funded researchers are attempting to differentiate very pure populations of mature cell types that can accelerate therapies.
Find Out More: Mark Mercola talks about differentiating cells into adult tissues (3:37)
Once a researcher has a mature cell type in a lab dish, the next step is to find out whether those cells can function in the body. For example, embryonic stem cells that have matured into insulin-producing cells in the lab are only useful if they continue producing insulin once transplanted inside a body. Likewise, researchers need to know that the cells can integrate into the surrounding tissue.
Scientists test cells by first developing an animal model that mimics the human disease, and then implanting the cells to see if they help treat the disease. These types of experiments can be painstakingbecause even if the cells dont completely cure the disease, they may restore some functions that would still be of enormous benefit to people. Researchers have to examine each of these possible outcomes.
In many cases testing the cells in a single animal model doesnt provide enough information. Most animal models of disease dont perfectly mimic the human disease. For example, a mouse carrying the same mutation that causes cystic fibrosis in humans doesnt show the same signs as a person with the disease. So, a stem cell therapy that treats this mouse model of cystic fibrosis may not work in humans. Thats why researchers often need to test the cells in many different animal models.
The promise of embryonic stem cells is that they can form any type of cell in the body. The trouble is that when implanted into an animal they do just that, in the form of tumors called teratomas. These tumors consist of a mass of many cells types and can include hair cells and many other tissues.
These teratomas are one reason why it is necessary to mature the embryonic stem cells into highly purified adult cell types before implanting into humans. Virtually all evidence has shown that the mature cells are restricted to their one identity and dont appear to revert to a teratoma-forming cell.
Find Out More: UC Davis researcher focuses on stem cell safety (from UC Davis) Paul Knoepfler talks about the tendency of embryonic stem cells to form tumors (4:10)
Transplanted stem cells, like any transplanted organ, can be recognized by the immune system as foreign and then rejected. In organ transplants such as liver, kidney, or heart, people must be on immune suppressive drugs for the rest of their lives to prevent the immune system from recognizing that organ as foreign and destroying it.
The likelihood of the immune system rejecting a transplant of embryonic stem cell-based tissue depends on the origin of that tissue. Stem cells isolated from IVF embryos will have a genetic makeup that will not match that of the person who receives the transplant. That persons immune system will recognize those cells as foreign and reject the tissue unless a person is on powerful immune suppressive drugs.
Stem cells generated through SCNT or iPS cell technology, on the other hand, are a perfect genetic match. The immune system would likely overlook that transplanted cells, seeing it as a normal part of the body. Still, some suggest that even if the cells are perfectly matched, they may not entirely escape the notice of the immune system. Cancer cells, for example, have the same genetic make up as surrounding tissue and yet the immune system will often identify and destroy early tumors. Until more information is available from animal studies it will be hard to know whether transplanted patient-specific cells are likely to call the attention of the immune system.
Find Out More: Jeffrey Bluestone talks about immune rejection of stem cell-based therapies (4:05)
In order to be approved by the FDA for use in human trials, stem cells must be grown in good manufacturing practice (GMP) conditions. Under GMP standards, a cell line has to be manufactured so that each group of cells is grown in an identical, repeatable, sterile environment. This ensures that each batch of cells has the same properties, and each person getting a stem cell therapy gets an equivalent treatment. Although the FDA hasnt yet issued guidelines for how pluripotent stem cells need to meet GMP standards, achieving this level of consistency could mean knowing the exact identity and quantity of every component involved in growing the cells.
Growing stem cells under strictly controlled conditions is still a challenge. Most stem cells are grown on feeder cells, a layer of animal or human cells on the lab dish that provide the nutrients the cells need to grow and divide. Scientists dont currently know what it is exactly that the feeder cells provide, and so the use of those feeder cells probably wont conform to GMP standards. CIRM is funding researchers who are trying to learn how to grow pluripotent stem cell lines in the absence of feeder cells, and to isolate new lines under GMP standards.
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The Power of Stem Cells | California’s Stem Cell Agency
The University of Rochester Stem Cell and Regenerative Medicine Institute was founded in 2008 in recognition of the tremendous promise that the discipline of stem cell biology offers for our understanding of development, disease and discovery of new treatments for a wide range of afflictions. Much as the discoveries of antibiotics and vaccination revolutionized our abilities to treat disease and reduce suffering, the discoveries of stem cell biology are poised to provide similar benefits
The University of Rochester is home to a rich and diverse stem cell faculty, with more than 40 faculty from 15 different departments, and more than 35 research track faculty and senior research fellows. These laboratories are collectively home to over 200 staff, including multiple Ph.D. students, postdoctoral fellows, M.D./Ph.D. students and technical fellows. Currently committed research awards, center grants, training grants and industry sponsored programs generated by this faculty represent over $60 million in direct cost commitments. Several of the programs at the University of Rochester Medical Center (URMC) are among the top programs both nationally and internationally. For example, there is particular strength in the field of neuromedicine, particularly in the context of the stem and progenitor cells giving rise to the glial cells of the central nervous system, with the faculty at URMC including several of the international leaders in such research. The Center for Musculoskeletal Research is rated as the No. 1 orthopaedics group in the United States in NIH funding. In the newly evolving field of cancer stem cell biology, a team of leading individuals also has been assembled, with drugs discovered through this effort already entering clinical trials. This intellectual environment is associated with large numbers of patent applications and with multiple opportunities for translating discoveries into therapies.
The research interests of faculty associated with University of Rochesters Stem Cell and Regenerative Medicine Institute range from model organisms to treatment of neurological disease, from investigations on the origins of red blood cells to the developing approaches to the treatment of fractures and osteroporosis, from studies on how to protect the body from the toxic effects of current cancer treatments to the development of new treatments that target cancer cells while sparing the normal cells of the body.
The following are recent news and events from our Institute:
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UR Stem Cell and Regenerative Medicine Institute (SCRMI)
Herbal medicine uses plants, or mixtures of plant extracts, to treat illness and promote health. It aims to restore your body’s ability to protect, regulate and heal itself. It is a whole body approach, so looks at your physical, mental and emotional well being. It is sometimes called phytomedicine, phytotherapy or botanical medicine.
The two most common types of herbal medicine used in the UK are Western herbal medicine and Chinese herbal medicine. Some herbalists practice less common types of herbal medicine such as Tibetan or Ayurvedic medicine (Indian).
Many modern drugs are made from plants. But herbalists dont extract plant substances in the way the drug industry does. Herbalists believe that the remedy works due to the delicate chemical balance of the whole plant, or mixtures of plants, not one particular active ingredient.
Western herbal medicine focuses on the whole person rather than their illness. So the herbalist looks at your personal health history, family history, diet and lifestyle. Herbalists use remedies made from whole plants, or plant parts, to help your body heal itself or reduce the side effects of medical treatments. Western herbal therapies are usually made from herbs that grow in Europe and North America but also use herbs from China and India.
Chinese herbal medicine is part of a whole system of medicine called Traditional Chinese Medicine (TCM) which includes
TCM aims to restore the balance of your Qi (pronounced chee). TCM practitioners believe that Qi is the flow of energy in your body, and is essential for good health. Chinese herbalists use plants according to their taste and how they affect a particular part of the body or an energy channel in the body. They may use a mixture of plants and other substances.
The Chinese remedy reference book used by TCM practitioners contains hundreds of medicinal substances. Most of the substances are plants but there are also some minerals and animal products. Practitioners may use different parts of plants such as the leaves, roots, stems, flowers or seeds. Usually, herbs are combined and you take them as teas, capsules, tinctures, or powders.
Herbal medicine | Cancer Research UK
(PHILADELPHIA) — In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania’s Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells. The protocol, which involves removing patients’ cells and modifying them in Penn’s vaccine production facility, then infusing the new cells back into the patient’s body following chemotherapy, provides a tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma. The findings, published simultaneously today in the New England Journal of Medicine and Science Translational Medicine, are the first demonstration of the use of gene transfer therapy to create “serial killer” T cells aimed at cancerous tumors.
“Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected,” said senior author Carl June, MD, director of Translational Research and a professor of Pathology and Laboratory Medicine in the Abramson Cancer Center, who led the work. “It worked much better than we thought it would.”
The results of the pilot trial of three patients are a stark contrast to existing therapies for CLL. The patients involved in the new study had few other treatment options. The only potential curative therapy would have involved a bone marrow transplant, a procedure which requires a lengthy hospitalization and carries at least a 20 percent mortality risk — and even then offers only about a 50 percent chance of a cure, at best.
“Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them,” says co-principal investigator David Porter, MD, professor of Medicine and director of Blood and Marrow Transplantation. “This approach has the potential to do the same thing, but in a safer manner.”
Secret Ingredients June thinks there were several “secret ingredients” that made the difference between the lackluster results that have been seen in previous trials with modified T cells and the remarkable responses seen in the current trial. The details of the new cancer immunotherapy are detailed in Science Translational Medicine.
After removing the patients’ cells, the team reprogrammed them to attack tumor cells by genetically modifying them using a lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19.
Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL tumor cells and normal B cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T cells, which limits side effects typically experienced during standard therapies.
The team engineered a signaling molecule into the part of the CAR that resides inside the cell. When it binds to CD19, initiating the cancer-cell death, it also tells the cell to produce cytokines that trigger other T cells to multiply — building a bigger and bigger army until all the target cells in the tumor are destroyed.
Serial Killers “We saw at least a 1000-fold increase in the number of modified T cells in each of the patients. Drugs don’t do that,” June says. “In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell led to the killing of thousands of tumor cells and overall, destroyed at least two pounds of tumor in each patient.”
The importance of the T cell self-replication is illustrated in the New England Journal of Medicine paper, which describes the response of one patient, a 64-year old man. Prior to his T cell treatment, his blood and marrow were replete with tumor cells. For the first two weeks after treatment, nothing seemed to change. Then on day 14, the patient began experiencing chills, nausea, and increasing fever, among other symptoms. Tests during that time showed an enormous increase in the number of T cells in his blood that led to a tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.
By day 28, the patient had recovered from the tumor lysis syndrome and his blood and marrow showed no evidence of leukemia.
“This massive killing of tumor is a direct proof of principle of the concept,” Porter says.
The Penn team pioneered the use of the HIV-derived vector in a clinical trial in 2003 in which they treated HIV patients with an antisense version of the virus. That trial demonstrated the safety of the lentiviral vector used in the present work.
The cell culture methods used in this trial reawaken T cells that have been suppressed by the leukemia and stimulate the generation of so-called “memory” T cells, which the team hopes will provide ongoing protection against recurrence. Although long-term viability of the treatment is unknown, the doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their seek-and-destroy mission against cancerous cells throughout the patients bodies.
Moving forward, the team plans to test the same CD19 CAR construct in patients with other types of CD19-positive tumors, including non-Hodgkin’s lymphoma and acute lymphocytic leukemia. They also plan to study the approach in pediatric leukemia patients who have failed standard therapy. Additionally, the team has engineered a CAR vector that binds to mesothelin, a protein expressed on the surface of mesothelioma cancer cells, as well as on ovarian and pancreatic cancer cells.
In addition to June and Porter, co-authors on the NEJM paper include Bruce Levine, Michael Kalos, and Adam Bagg, all from Penn Medicine. Michael Kalos and Bruce Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include June, Porter, Sharyn Katz and Adam Bagg from Penn and Stephan Grupp the Children’s Hospital of Philadelphia.
The work was supported by the Alliance for Cancer Gene Therapy, a foundation started by Penn graduates Barbara and Edward Netter, to promote gene therapy research to treat cancer, and the Leukemia & Lymphoma Society.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according toU.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top “Honor Roll” hospitals byU.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided$814million to benefit our community.
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Researchers and physicians are studying how to regenerate beta cells in the lab and within the pancreas, which may lead to new treatments for type 1 and type 2 diabetes.
Beta cell dysfunction is a characteristic of both type 1 and type 2 diabetes. In type 1 diabetes, beta cells insulin-producing cells found in the pancreas are destroyed, while in type 2 diabetes, they may not produce enough insulin.
Since it’s not possible today to generate new, patient-specific, functional beta cells, people with type 1 diabetes need insulin therapy. People with type 2 diabetes often need medications, with certain cases requiring insulin therapy.
Center for Regenerative Medicine researchers, led by Yasuhiro Ikeda, D.V.M., Ph.D., and Yogish C. Kudva, MBBS, both of Mayo Clinic in Rochester, Minn., are taking two related approaches to beta cell regeneration that may lead to new treatments for diabetes.
In the laboratory. In vitro beta cell regeneration uses induced pluripotent stem (iPS) cells, a type of bioengineered stem cell that acts like an embryonic stem cell. Using a person’s own skin cells or blood cells as a starting point, Mayo researchers have successfully generated patient-specific iPS cells and subsequently converted them into glucose-responsive, insulin-producing cells in the laboratory.
Once fully optimized, such cells may enable a novel cell therapy for beta cell dysfunction in diabetes. And since the transplanted cells are derived from the patient’s own cells, there would be no need to give the patient any immunosuppressive drugs, which are necessary for pancreas and islet cell transplants today.
In a patient’s own pancreas. Mayo researchers are working to enhance a person’s natural ability to regenerate beta cells using gene therapy, which involves delivering to the pancreas cellular factors known to enhance beta cell growth and regeneration.
Investigators have developed pancreatic beta cell- and exocrine tissue-specific gene delivery vectors, and they are now studying the therapeutic effects of pancreatic overexpression of beta cell regenerating factors.
Recent results have shown that pancreatic delivery of a synthesized artificial fusion protein can prevent diabetes development in drug-induced diabetic mice. Several other strategies are also being evaluated.
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Beta cell regeneration – Center for Regenerative Medicine …
Research has shown that cancer cells are not all the same. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term.
The idea that cancer is primarily driven by a smaller population of stem cells has important implications. For instance, many new anti-cancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalksbut no matter how low the weeks are cut, if the roots arent taken out, the weeds will just grow back.
Another important implication is that it is the cancer stem cells that give rise to metastases (when cancer travels from one part of the body to another) and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation or chemotherapy has eliminated all observable signs of a cancer.
One component of the cancer stem cell theory concerns how cancers arise. In order for a cell to become cancerous, it must undergo a significant number of essential changes in the DNA sequences that regulate the cell. Conventional cancer theory is that any cell in the body can undergo these changes and become a cancerous outlaw. But researchers at the Ludwig Center observe that our normal stem cells are the only cells that reproduce themselves and are therefore around long enough to accumulate all the necessary changes to produce cancer. The theory, therefore, is that cancer stem cells arise out of normal stem cells or the precursor cells that normal stem cells produce.
Thus, another important implication of the cancer stem cell theory is that cancer stem cells are closely related to normal stem cells and will share many of the behaviors and features of those normal stem cells. The other cancer cells produced by cancer stem cells should follow many of the rules observed by daughter cells in normal tissues. Some researchers say that cancerous cells are like a caricature of normal cells: they display many of the same features as normal tissues, but in a distorted way. If this is true, then we can use what we know about normal stem cells to identify and attack cancer stem cells and the malignant cells they produce. One recent success illustrating this approach is research on anti-CD47 therapy.
Next Section >> Case Study: Leukemia
The Stem Cell Theory of Cancer – Stanford Medicine Center
Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the bodys hereditary material and can make copies of themselves.
Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell. Human cells contain the following major parts, listed in alphabetical order:
Within cells, the cytoplasm is made up of a jelly-like fluid (called the cytosol) and other structures that surround the nucleus.
The cytoskeleton is a network of long fibers that make up the cells structural framework. The cytoskeleton has several critical functions, including determining cell shape, participating in cell division, and allowing cells to move. It also provides a track-like system that directs the movement of organelles and other substances within cells.
This organelle helps process molecules created by the cell. The endoplasmic reticulum also transports these molecules to their specific destinations either inside or outside the cell.
The Golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.
These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components.
Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves.
The nucleus serves as the cells command center, sending directions to the cell to grow, mature, divide, or die. It also houses DNA (deoxyribonucleic acid), the cells hereditary material. The nucleus is surrounded by a membrane called the nuclear envelope, which protects the DNA and separates the nucleus from the rest of the cell.
The plasma membrane is the outer lining of the cell. It separates the cell from its environment and allows materials to enter and leave the cell.
Ribosomes are organelles that process the cells genetic instructions to create proteins. These organelles can float freely in the cytoplasm or be connected to the endoplasmic reticulum (see above).
The Genetic Science Learning Center at the University of Utah offers an interactive introduction to cells and their many functions.
Nature Educations Scitable explains what cells are made of and how they originated in their fact sheet What is a Cell?
Arizona State Universitys Ask a Biologist provides a description and illustration of each of the cells organelles.
Queen Mary University of London allows you to explore a 3-D cell and its parts.
Additional information about the cytoskeleton, including an illustration, is available from the Cytoplasm Tutorial. This resource is part of The Biology Project at the University of Arizona.
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What is a cell? – Genetics Home Reference
Learn more about Cell Therapy & Regenerative Medicine.
What is a Neurosphere?
CTRM provides services to develop and manufacture novel cellular therapy.
The Cell Therapy and Regenerative Medicine Program (CTRM) at the University of Utah provides the safest, highest quality products for therapeutic use and research. Our goals are to facilitate the availability of cellular and tissue based therapies to patients by bridging efforts in basic research, bioengineering and the medical sciences. As well as assemble the expertise and infrastructure to address the complex regulatory, financial and manufacturing challenges associated with delivering cell and tissue based products to patients.
To support hematopoietic stem cell transplants and to deliver innovative cellular and tissue engineered products to patients by providing comprehensive bench to bedside services that coordinate the efforts of clinicians, researchers, and bioengineers.
Product quality, safety and efficacy; Optimization of resource utilization; Promotion of productive collaborations; Support of innovative products; and Adherence to scientific and ethical excellence.
The Center of Excellence for the state of Utah that translates cutting-edge cell therapy and engineered tissue based research into clinical products that extend and improve the quality of life of individuals suffering from debilitating diseases and injuries.
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Cell Therapy & Regenerative Medicine – University of Utah …
Sickle cell anemia (SCD) facts
Sickle cell anemia (sickle cell disease) is a disorder of the blood caused by an inherited abnormal hemoglobin (the oxygen-carrying protein within the red blood cells). The abnormal hemoglobin causes distorted (sickled) red blood cells. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. This condition is referred to as sickle cell anemia. The irregular sickled cells can also block blood vessels causing tissue and organ damage and pain.
Sickle cell anemia is one of the most common inherited blood anemias. The disease primarily affects Africans and African Americans. It is estimated that in the United States, some 90,000 to 100,000 Americans are afflicted with sickle cell anemia. Overall, current estimates are that one in 500 U.S. African American births is affected with sickle cell anemia.
Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition. This means that the gene can be passed on from a parent carrying it to male and female children. In order for sickle cell anemia to occur, a sickle cell gene must be inherited from both the mother and the father, so that the child has two sickle cell genes.
The inheritance of just one sickle gene is called sickle cell trait or the “carrier” state. Sickle cell trait does not cause sickle cell anemia. Persons with sickle cell trait usually do not have many symptoms of disease and have hospitalization rates and life expectancies identical to unaffected people. When two carriers of sickle cell trait mate, their offspring have a one in four chance of having sickle cell anemia. (In some parts of Africa, one in five persons is a carrier for sickle cell trait.)
Medically Reviewed by a Doctor on 5/21/2015
Sickle Cell Disease (Sickle Cell Anemia) – Experience Question: Please describe your experience with sickle cell disease (sickle cell anemia).
Sickle Cell Disease (Anemia) – Diagnosis Question: How was your sickle cell anemia diagnosed?
Sickle Cell Disease (Sickle Cell Anemia) – Symptoms Question: At what age did symptoms of sickle cell anemia first appear in someone you know? Please describe other symptoms.
Red blood cells are manufactured in the bone marrow. Their unique biconcave shape (think of squeezing a marshmallow between your fingers) increases their storage capacity for hemoglobin molecules that carry oxygen. They also make the cells pliable and soft so they can squeeze through the tiniest blood vessels in the body. In sickle disease, the red blood cells form an abnormal crescent shape that is rigid, causing the red blood cells to be damaged. The cells aren’t malleable enough to get through tight spaces, and this can increase the risk of forming blood clots in the small capillaries of different organs causing the potential for organ damage.
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Sickle Cell Anemia: Learn About SCD Symptoms and Treatment
Every one of us completely regenerates our own skin every 7 days. A cut heals itself and disappears in a week or two. Every single cell in our skeleton is replaced every 7 years.
The future of medicine lies in understanding how the body creates itself out of a single cell and the mechanisms by which it renews itself throughout life.
When we achieve this goal, we will be able to replace damaged tissues and help the body regenerate itself, potentially curing or easing the suffering of those afflicted by disorders like heart disease, Alzheimers, Parkinsons, diabetes, spinal cord injury and cancer.
Research at the institute leverages Stanfords many strengths in a way that promotes that goal. The institute brings together experts from a wide range of scientific and medical fields to create a fertile, multidisciplinary research environment.
There are four major research areas of emphasis at the institute:
Theres no way to know, beforehand, which particular avenue of stem cell research will most expediently yield a successful treatment or cure. Therefore, we need to vigorously pursue a broad number of promising leads concurrently.
–Philip A. Pizzo, MD Carl and Elizabeth Naumann Professor Dean, Stanford University School of Medicine
What are the symptoms and treatments of sickle cell anemia?
Virtually all of the major symptoms of sickle cell anemia are the direct result of the abnormally shaped, sickled red blood cells blocking the flow of blood that circulates through the tissues of the body. The tissues with impaired circulation suffer damage from lack of oxygen. Damage to tissues and organs of the body can cause severe disability in patients with sickle cell anemia. The patients endure episodes of intermittent “crises” of variable frequency and severity, depending on the degree of organ involvement.
The major features and symptoms of sickle cell anemia include:
Some features of sickle cell anemia, such as fatigue, anemia, pain crises, and bone infarcts can occur at any age. Many features typically occur in certain age groups.
Sickle cell anemia usually first presents in the first year of life. Infants and younger children can suffer with fever, abdominal pain, pneumococcal bacterial infections, painful swellings of the hands and feet (dactylitis), and splenic sequestration. Adolescents and young adults more commonly develop leg ulcers, aseptic necrosis, and eye damage. Symptoms in adult typically are intermittent pain episodes due to injury of bone, muscle, or internal organs.
Affected infants do not develop symptoms in the first few months of life because the hemoglobin produced by the developing fetus (fetal hemoglobin) protects the red blood cells from sickling. This fetal hemoglobin is absent in the red blood cells that are produced after birth so that by 5 months of age, the sickling of the red blood cells is prominent and symptoms begin.
The treatment of sickle cell anemia is directed to the individual features of the illness present. In general treatment is directed at the management and prevention of the acute manifestations as well as therapies directed toward blocking the red blood cells from stacking together. There is no single remedy to reverse the anemia. It is, therefore, important that affected individuals and their family members have an optimal understanding of the illness and that communication with the doctors and medical personnel be maintained.
Fatigue is a common symptom in persons with sickle cell anemia. Sickle cell anemia causes a chronic form of anemia which can lead to fatigue. The sickled red blood cells are prone to breakage (hemolysis) which causes reduced red blood cell life span (the normal life span of a red blood cell is 120 days). These sickled red blood cells are easily detected with a microscope examination of a smear of blood on a glass slide.
Typically, the site of red blood cell production (bone marrow) works overtime to produce these cells rapidly, attempting to compensate for their destruction in the circulation. Occasionally, the bone marrow suddenly stops producing the red blood cells which causes a very severe form of anemia (aplastic crises). Aplastic crises can be promoted by infections that otherwise would seem less significant, including viruses of the stomach and bowels and the flu (influenza).
The anemia of sickle cell anemia tends to stabilize without specific treatments. The degree of anemia is defined by measurement of the blood hemoglobin level. Hemoglobin is the protein molecule in red blood cells which carries oxygen from the lungs to the body’s tissues and returns carbon dioxide from the tissues to the lungs. Blood hemoglobin levels in persons with sickle cell anemia are generally between 6 to 8 gms/dl (normal levels are above 11 gms/dl). Occasionally, there can be a severe drop in hemoglobin requiring a blood transfusion to correct the anemia (such as in patients suffering splenic sequestration). Blood transfusion is usually reserved for those patients with other complications, including pneumonia, lung infarction, stroke, severe leg ulceration, or late pregnancy. (Among the risks of blood transfusion are hepatitis, infection, immune reaction, and injury to body tissues from iron overload.) Transfusions are also given to patients to prepare them for surgical procedures. Folic acid is given as a supplement. Sometimes a red blood cell exchange is performed. This process removes some of the sickle blood cells and replaces them with normal (non-sickle) blood cells. It is done when the sickle cell crisis is so sever that other forms of treatment are not helping.
Pain crises in persons with sickle cell anemia are intermittent painful episodes that are the result of inadequate blood supply to body tissues. The impaired circulation is caused by the blockage of various blood vessels from the sickling of red blood cells. The sickled red blood cells slow or completely impede the normal flow of blood through the tissues. This leads to excruciating pain, often requiring hospitalization and opiate medication for relief. The pain typically is throbbing and can change its location from one body area to another. Bones are frequently affected. Pain in the abdomen with tenderness is common and can mimic appendicitis. Fever frequently is associated with the pain crises.
A pain crisis can be promoted by preceding dehydration, infection, injury, cold exposure, emotional stress, or strenuous exercise. As a prevention measure, persons with sickle cell anemia should avoid extremes of heat and cold.
Pain crises require analgesia for pain and increased fluid intake. Dehydration must be prevented to avoid further injury to the tissues and intravenous fluids can be necessary. Along with the fluids clotrimazole and magnesium are often given. Other modalities, such as biofeedback, self-hypnosis, and/or electrical nerve stimulation may be helpful.
Hydroxyurea is a medication that is currently being used in adults and children with severe pain from sickle cell anemia. It is also considered for those with recurrent strokes and frequent transfusions. This drug acts by increasing the amount of fetal hemoglobin in the blood (this form of hemoglobin is resistant to sickling of the red blood cells). The response to hydroxyurea is variable and unpredictable from patient to patient. Hydroxyurea can be suppressive to the bone marrow.
Swelling and inflammation of the hands and/or feet is often an early sign of sickle cell anemia. The swelling involves entire fingers and/or toes and is called dactylitis. Dactylitis is caused by injury to the bones of the affected digits by repeated episodes of inadequate blood circulation. Dactylitis generally occurs in children with sickle cell anemia from age 6 months to 8 years.
Joint inflammation (arthritis) with pain, swelling, tenderness, and limited range of motion can accompany the dactylitis. Sometimes, not only the joints of the hands or feet are affected, but also a knee or an elbow.
The inflammation from dactylitis and arthritis can be reduced by anti-inflammation medications, such as ibuprofen and aspirin.
Lung infection (pneumonia) is extremely common in children with sickle cell anemia and is also the most common reason for hospitalization. Pneumonia can be slow to respond to antibiotics. The type of bacteria that is frequently the cause of pneumonia is called the pneumococcus. (This is, in part, due to the increased susceptibility to this particular bacteria when the spleen is poorly functioning.) Vaccination against pneumococcal infection is generally recommended.
Children with sickle cell anemia are also at risk for infection of the brain and spinal fluid (meningitis). Bacteria that are frequent causes of this infection include the Pneumococcus and Haemophilus bacteria.
Furthermore, children with sickle cell anemia are at risk for an unusual form of bone infection (osteomyelitis). The infection is typically from a bacteria called Salmonella.
Bacterial infections can be serious and even overwhelming for patients with sickle cell anemia. Early detection and antibiotic treatment are the keys to minimizing complications. Any child with sickle cell anemia must be evaluated by medical professionals when fever or other signs of infection (such as unexplained pain or cough) appear.
Over time, the spleen can become damaged and stop working, which increases the risk of developing various severe infections.
It has been demonstrated that the liver, and especially the spleen, are organs that are very active in removing sickled red blood cells from the circulation of persons with sickle cell anemia. This process can accelerate suddenly. Sudden pooling of blood in the spleen is referred to as splenic sequestration.
Splenic sequestration can cause very severe anemia and even result in death.
The spleen is commonly enlarged (splenomegaly) in younger children with sickle cell anemia. As the spleen is repeatedly injured by damage from impaired blood supply, it gradually shrinks with scarring. Impairment of the normal function of the spleen increases the tendency to become infected with bacteria.
Sudden pooling of blood in the spleen (splenic sequestration) can result in a very severe anemia and death. These patients can develop shock and lose consciousness. Transfusion of blood and fluids can be critical if this occurs.
Liver enlargement (hepatomegaly) occurs as it becomes congested with red blood cells as well. The liver is often firm and can become tender. Impaired liver function can result in yellowing of the eyes (jaundice). The gallbladder, which drains bile from the liver, can fill with gallstones. Inflammation of the gallbladder (cholecystitis) can cause nausea and vomiting and require its removal.
Aside from lung infection (pneumonia), the lungs of children with sickle cell anemia can also be injured by inadequate circulation of blood which causes areas of tissue death. This lung damage can be difficult to distinguish from pneumonia and is known as acute chest syndrome. These localized areas of lung tissue damage are referred to as pulmonary infarcts. Pulmonary infarcts often require a special x-ray test using a dye injected into the affected areas (angiogram) for diagnosis. Repeated pulmonary infarcts can lead to scarring of the lungs of children with sickle cell anemia by the time they reach adolescence.
The heart is frequently enlarged in children with sickle cell anemia. Rapid heart rates and murmurs are common. The heart muscle can also be injured by infarcts and iron depositing in the muscle as it leaks from the ruptured red blood cells. Over time, the heart muscle weakens and the heart pumps blood more and more poorly.
Injuries to the lungs or heart are treated according to the specific type of damage and the degree of impairment of organ function. Supplementary oxygen can be required. Infections of the lungs require aggressive antibiotics. Transfusions can sometimes help prevent further damage to the lung tissue. Heart failure can require medications to assist the heart in more effectively pumping blood to the body.
The legs of patients with sickle cell anemia are susceptible to skin breakdown and ulceration. This seems to be a result of the stagnant blood flow caused by the sickled red blood cells. Injury to the skin of the legs or ankles can promote skin damage and ulceration.
Leg ulcers most commonly occur in adults and usually form over the ankles and sides of the lower legs. The ulcers can become severe, even encircling the leg, and are prone to infection.
Leg ulcers can become chronic and resistant to many treatments. Oral antibiotics and topical creams are often used. Elevation of the leg, careful dressing changes, and other topical therapies can be helpful. Some ulcers can be so resistant that skin grafting is recommended, though this may be compromised by impaired healing.
Inadequate circulation of the blood, which is characteristic of sickle cell anemia, also causes areas of death of bone tissue (bone infarction). Aseptic necrosis, or localized bone death, is a result of inadequate oxygen supply to the bone. Aseptic necrosis is also referred to as osteonecrosis.
While virtually any bone can be affected, the most common are the bones of the thighs, legs, and arms. The result can permanently damage or deform the hips, shoulders, or knees. Pain, tenderness, and disability frequently are signs of aseptic necrosis. Painful bone infarcts can be relieved by rest and pain medications.
Aseptic necrosis can permanently damage large joints (such as the hips or shoulders). Local pain can be relieved and worsening of the condition can be prevented by avoiding weight bearing. With more severe damage, total joint replacement may be needed to restore function.
The critical area of the eye that normally senses light is called the retina. The retina is in the back of the eye and is nourished by many tiny blood vessels. Impairment of the circulation from the sickling of red blood cells results in damage to the retina (retinopathy). The result can be partial or complete blindness.
Bleeding can also occur within the eye (retinal hemorrhage) and retinal detachment can result. Retinal detachment can lead to blindness.
Once blindness occurs, it is usually permanent. Preventative measures, such as laser treatments, can be used if bleeding into the eye and retinal detachment are detected early.
Additional features of sickle cell anemia include weakening of bones from osteoporosis, kidney damage and infection, and nervous system damage. Osteoporosis can lead to severe pain in the back and deformity from collapse of the spine (vertebrae). Kidney damage can lead to poor kidney function with a resulting imbalance of blood sodium and acidity as well as bleeding into the urine. Kidney infection can cause pelvic pain and require hospitalization with antibiotic treatment. Injury to the nervous system can result from meningitis or sickle cell anemia itself. Poor blood circulation in the brain can cause stroke, convulsions, and coma.
Damage to the brain from stroke can cause permanent loss of function to areas of the body. Transfusion of blood and fluids intravenously can be critical. Medications to reduce the chance of seizures are sometimes added. If stroke results in long-term impairment of function, physical therapy, speech therapy, and occupational therapy can be helpful.
Priapism, an abnormally persistent erection of the penis in the absence of sexual desire, can occur in persons with sickle cell anemia. Priapism can lead to impotence and damage to affected tissues.
Medically Reviewed by a Doctor on 5/21/2015
Sickle Cell Disease (Sickle Cell Anemia) – Experience Question: Please describe your experience with sickle cell disease (sickle cell anemia).
Sickle Cell Disease (Anemia) – Diagnosis Question: How was your sickle cell anemia diagnosed?
Sickle Cell Disease (Sickle Cell Anemia) – Symptoms Question: At what age did symptoms of sickle cell anemia first appear in someone you know? Please describe other symptoms.
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Sickle Cell Disease (Sickle Cell Anemia … – MedicineNet
CTL019 is a clinical trial of T cell therapyfor patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL). At this time, The Children’s Hospital of Philadelphia is the only hospital enrolling pediatric patientson this trial.
In July 2014, CTL019 was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy is the first personalized cellular therapy for the treatment of cancer to receive this important classification.
In this clinical trial, immune cells called T cells are taken from a patient’s own blood. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. This is how T cell therapy works:
30 patients with acute lymphoblastic leukemia (25 children and 5 adults) have been treatedusing T cell therapy.Of those patients:
The most recent results were published in The New England Journal of Medicine in October 2014. Scientists at The Childrens Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, and because those patients have been followed for a relatively shorttime,it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response, and maintain that response.
At this point CHOP’s capability to enroll patients is limited because of the need to manufacture the T cell product used in this therapy. Our goal is to boost enrollment soon, by increasing our manufacturing capabilities and by broadening this study to other pediatric hospitals.
T cell therapy is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. It is an option for those patients who have very resistant ALL.
Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients whose leukemia is not responding to chemotherapy,and whose disease has come back after a bone marrow transplant.
It is important to note that while results of this study are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.
Referring physicians and families are encouraged to consider the potential benefits of clinical trials early in the cancer treatment process. In the case of CTL019 and other cell therapies, it is critical that cells are collected from the patient before they are too sick. Also, intensive chemotherapy will decrease the number of normal T cells we need to collect from the patient.
While most childhood cancers are cured by standard treatment protocols, learning about the many new experimental therapies available at CHOP soon after diagnosis may keep more options open for patients who relapse.
Stephan Grupp, MD, PhD, leads CTL019 efforts at The Childrens Hospital of Philadelphia. His research builds on an ongoing collaboration with the team that originally designed the CTL019 cells as a treatment for B cell leukemias, and first used the cell therapy against chronic lymphocytic leukemia (CLL) in adults.
Richard Aplenc, MD, PhD, MSCE, and Susan Rheingold, MD,are the first points of contact for any pediatric patient considering T cell therapy,andwill help families navigate the process of coming to CHOP for a second opinion. These CHOP oncologists are among the nation’s leading experts in pediatric leukemia.
Carl H. June, MD, of the Perelman School of Medicine at the University of Pennsylvania, led the research group that announced unprecedented results in August 2011 in treating three adult patients with advanced cases of CLL.
Dr. Grupp and his colleagues adapted the CTL019 treatment to combat ALL, the most common childhood cancer. Initial results of this clinical trial were published by The New England Journal of Medicine on March 25, 2013.
The CTL019 therapy represents a new approach to cancer treatment called immunotherapy or cell therapy. The idea behind immunotherapy is to use our bodies own immune cells, which fight infection, to kill off cancer cells.
Cancer researchers have spent more than a decade studying immunotherapy as a possible treatment for cancer. Over the years they solved many of the problems associated with this type of treatment, including learning how to induce the cells to recognize cancer and how to grow cells in a lab in way that it would be safe to re-infuse them into patients.
The final hurdle in this research was the most difficult to jump: learning how to engineer a cell that would continue to grow in the body for more than a few days, and then remain in the body for an extended period of time to continue controlling a patients disease for the long-term. CTL019 reflects a solution to this last problem, making the trial unique compared to earlier forms of cell therapy.
In using CTL019 cells to treat his first pediatric patient, Dr. Grupp found that the very activity that destroyed leukemia cells also stimulated a highly activated immune response called cytokine release syndrome. The child became very ill and had to be admitted to the intensive care unit.
Dr. Grupp and his team decided to counteract these toxic side effects by using two immunomodulating drugs that blunted the overactive immune response and rapidly relieved the childs treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019 treatments for adults as well.
Dr. Grupp presented an abstract describing this treatment of CTL019-associated cytokine release syndrome at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2012.
Stemcentrx scientists working with targeted molecules that can kill some types of lung cancer. MIT Tech Review Image.
A stem cell biotech in the news this week was one thathad mostly flown under the radar previously.
Stemcentrx hasa focus on killing cancer stem cells as a novel approach to treating cancer. Antonio Regalado had a nice articleyesterday on the company. He reports that Stemcentrx has around a half a billion in funding. It is valued in the billions. These are very unusual figures for a stem cell biotech.
Stemcentrx isdeveloping novel cancer therapeutics such as antibodies that target cancer stem cells. Their development pipeline at least in part uses a model of serial xenograft tumor transplantation in mice.Cancer stem cells are also sometimes called tumor initiating cells (TIC). As a cancer stem cell researcher myself, I find Stemcentrx intriguing.
The company published an encouraging bit of preclinical data recently in Science Translational Medicinewith a team of authors including leading company scientist, Scott Dylla. In this paper the team presented evidence that they have a product in the form of a loaded antibody (conjugated to a toxin) against a molecule called DLL3 important to TIC biological function and survival. DLL3 is part of the Notch signaling pathway. Stay tuned tomorrow for my interview with Dr. Dylla.
They showed that this anti-DLL3 antibody,SC16LD6.5, exhibited anti-tumor activities in xenograft models of pulmonary neuroendocrine tumors such as small cell lung cancer. The company also has a clinical trial ongoing but not currently recruiting using this drug, and they have another trial for ovarian cancer based on antibody targeting as well.
SC16LD6.5 also exhibited some degree of toxicity in rats and a non-human primate model so thats a possible issue moving forward, but the toxic effects were at least partially reversible and when youre dealing with a deadly disease some toxicity for treatment is kind of to be expected.
Can Stemcentrx survive and hopefully even thrive as a company selling products that kill cancer stem cells? Well have a clearer picture on this in a few years, but in general biotechs of this type in this arena have a high failure rate. We need to keep in mind the long, sobering path ahead between these kinds of preclinical result and getting an approved drug to patients.
At the same time, this team has the money and talent to potentially succeed, and again, theres that half a billion in funding, which all by itself makes this stem cell biotech noordinary company. Theres another unique thing going on here: famed tech investor Peter Thiel is one of the major funders of the company.
Those of us in the cancer stem cell field have long been engaged in the debate overwhether these special cells exist in specific solid tumors and their functions in tumorigenesis. I believe they are present and important in some, but not all of such tumors. The controversial nature of TICs in lung cancer specifically makes SC16LD6.5 a high-risk, high reward kind ofproduct.
More weapons against lung cancer will be of coursea good thing and targeting cancer stem cells is an innovative approach. The company isrecruiting for many positions including scientists so if you are interested take a look.
I hope Stemcentrx succeeds and I look forward to reading more of their work as the years go by.
The winner of the inaugural Ogawa-Yamanaka Prize is Dr. Masayo Takahashi, MD, PhD.
According to the Gladstone Institutepress release, Dr. Takahashi was awarded the prize for her trailblazing work leading the first clinical trial to use induced pluripotent stem (iPS) cells in humans.
The prize, including a $150,000 cash award, will be given at a ceremony next week at the Gladstone on September 16. If you are interested in listening in, you can register for the webcast here.
Dr. Takahashi started the first ever human clinical study using iPS cells, which is focused on treating of macular degeneration using retinal pigmented epithelial cells derived from human iPS cells.
Congratulations to Dr. Takahashi for the great and well-deserved honor of the Ogawa-Yamanaka Prize.
As readers of this blog likely recall, Dr. Takahashi received our blogsStem Cell Person of the Year Award last year in honor of her pioneering work and that included a $2,000 prize.
Otherpast winners of our Stem Cell Person of the Year Award have gone on to get additional awards too.
The 2013 Stem Cell Person of the Year, Dr. Elena Cattaneo, went on to win the ISSCR Public Service Award in 2014 along with colleagues.
And our 2012 Stem Cell Person of the Year Award winner, stellar patient advocateRoman Reed, went on in 2013 to receive the GPI Stem Cell Inspiration Award.
The more we can recognize the pioneers and outside-the-box thinkers in the stem cell field, the better.
I recently ran a poll on my blog about how the FDA is doing on handling stem cell clinics.
There is substantial debate in the stem cell arena about how the FDA handles stem cell clinics ranging from the view that the agency is far too strict to excessively lenient.
The results of the poll reflect a great deal of dissatisfaction with the job that the FDA is doing on stem cell clinics.
Only 9% of respondents felt that the FDA is currently do things just about right.
While the top 2 answers were polar extremes, by a large margin the top answer was that the FDA was much too lenient.
Although Internet polls of this kind are not scientific, they can reflect sentiments of a community.
Science can come in various forms ranging from numbers to words to images.
In the stem cell field, some of the images can be particularly striking. One of my own favorites is the one above that I took some years ago of differentiation of neural stem cells that ended up on the cover of my first book.
Do you have a favorite stem cell-related image?
Im doing a stem cell image contest.
The winner receives a $100 prize and their image will be posted here along with a blurb on their research.
If more than one entry is particularly amazing, I may give out more than one prize.
The rules are straightforward. Anyone can enter whether you are in academia or industry.
Email me your favorite stem cell-related image (knoepflerATucdavisDOTedu). The image must be your own. Team entries are allowed.
By entering the contest you agree that the image may be posted on this stem cell blog.
The deadline is September 30th at midnight USA PDT.
As readers of this blog may recall, I have a garden where I grow a variety of plants every year. One year I had quite a few sunflowers and ever since I have volunteer sunflowers popping up that have all kinds of interesting traits. The neighborhood squirrels collected hundreds of sunflower seeds and buried some as a cache. Some of those survived and sprouted new sunflowers.and so on every year.
Ive noticed that each of the sunflowers becomes its own microcosm with thousands of bugs.
Predominantly each sunflower is colonized by ants, which farm aphids on them. However, other bugs live there too including some amazing praying mantises that hunt bees once they grow large enough.
You can see one at left from a past year. I thought to myself, Youre never going to catch a bee, but that mantis was big and fearless and there were a lot of bees.
This year Ive been following an interesting, very large yellow-green spider (anyone know what type it is?) who lives on a sunflower in the garden.
The spider hung out on the flower head too just like the mantises of past years. See below and look at the top of the sunflower. The spider almost looks like a crab. On the opposite side is a ladybug down around 6 oclock.
I wondered if the spider was hunting some insect attracted to the sunflower. Bees like the mantis? It isa very big spider so I was guessing it was eating well on something.
A few days later I took a look again and was impressed to see that the spider had caught a big bee.
What a meal!
Im still not sure on how the spider did it since it doesnt seem to be a web spinner. It must have been an ambush attack with maybe a quick loop of silk around the bee and some powerful venom.
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Knoepfler Lab Stem Cell Blog | Building innovative …
Cell culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. In practice, the term “cell culture” now refers to the culturing of cells derived from multicellular eukaryotes, especially animal cells, in contrast with other types of culture that also grow cells, such as plant tissue culture, fungal culture, and microbiological culture (of microbes). The historical development and methods of cell culture are closely interrelated to those of tissue culture and organ culture. Viral culture is also related, with cells as hosts for the viruses.
The laboratory technique of maintaining live cell lines (a population of cells descended from a single cell and containing the same genetic makeup) separated from their original tissue source became more robust in the middle 20th century.
The 19th-century English physiologist Sydney Ringer developed salt solutions containing the chlorides of sodium, potassium, calcium and magnesium suitable for maintaining the beating of an isolated animal heart outside of the body. In 1885, Wilhelm Roux removed a portion of the medullary plate of an embryonic chicken and maintained it in a warm saline solution for several days, establishing the principle of tissue culture.Ross Granville Harrison, working at Johns Hopkins Medical School and then at Yale University, published results of his experiments from 1907 to 1910, establishing the methodology of tissue culture.
Cell culture techniques were advanced significantly in the 1940s and 1950s to support research in virology. Growing viruses in cell cultures allowed preparation of purified viruses for the manufacture of vaccines. The injectable polio vaccine developed by Jonas Salk was one of the first products mass-produced using cell culture techniques. This vaccine was made possible by the cell culture research of John Franklin Enders, Thomas Huckle Weller, and Frederick Chapman Robbins, who were awarded a Nobel Prize for their discovery of a method of growing the virus in monkey kidney cell cultures.
Cells can be isolated from tissues for ex vivo culture in several ways. Cells can be easily purified from blood; however, only the white cells are capable of growth in culture. Mononuclear cells can be released from soft tissues by enzymatic digestion with enzymes such as collagenase, trypsin, or pronase, which break down the extracellular matrix. Alternatively, pieces of tissue can be placed in growth media, and the cells that grow out are available for culture. This method is known as explant culture.
Cells that are cultured directly from a subject are known as primary cells. With the exception of some derived from tumors, most primary cell cultures have limited lifespan.
An established or immortalized cell line has acquired the ability to proliferate indefinitely either through random mutation or deliberate modification, such as artificial expression of the telomerase gene. Numerous cell lines are well established as representative of particular cell types.
For the majority of isolated primary cells, they undergo the process of senescence and stop dividing after a certain number of population doublings while generally retaining their viability (described as the Hayflick limit).
Cells are grown and maintained at an appropriate temperature and gas mixture (typically, 37C, 5% CO2 for mammalian cells) in a cell incubator. Culture conditions vary widely for each cell type, and variation of conditions for a particular cell type can result in different phenotypes.
Aside from temperature and gas mixture, the most commonly varied factor in culture systems is the cell growth medium. Recipes for growth media can vary in pH, glucose concentration, growth factors, and the presence of other nutrients. The growth factors used to supplement media are often derived from the serum of animal blood, such as fetal bovine serum (FBS), bovine calf serum, equine serum, and porcine serum. One complication of these blood-derived ingredients is the potential for contamination of the culture with viruses or prions, particularly in medical biotechnology applications. Current practice is to minimize or eliminate the use of these ingredients wherever possible and use human platelet lysate (hPL). This eliminates the worry of cross-species contamination when using FBS with human cells. hPL has emerged as a safe and reliable alternative as a direct replacement for FBS or other animal serum. In addition, chemically defined media can be used to eliminate any serum trace (human or animal), but this cannot always be accomplished with different cell types. Alternative strategies involve sourcing the animal blood from countries with minimum BSE/TSE risk, such as The United States, Australia and New Zealand, and using purified nutrient concentrates derived from serum in place of whole animal serum for cell culture.
Plating density (number of cells per volume of culture medium) plays a critical role for some cell types. For example, a lower plating density makes granulosa cells exhibit estrogen production, while a higher plating density makes them appear as progesterone-producing theca lutein cells.
Cells can be grown either in suspension or adherent cultures. Some cells naturally live in suspension, without being attached to a surface, such as cells that exist in the bloodstream. There are also cell lines that have been modified to be able to survive in suspension cultures so they can be grown to a higher density than adherent conditions would allow. Adherent cells require a surface, such as tissue culture plastic or microcarrier, which may be coated with extracellular matrix (such as collagen and laminin) components to increase adhesion properties and provide other signals needed for growth and differentiation. Most cells derived from solid tissues are adherent. Another type of adherent culture is organotypic culture, which involves growing cells in a three-dimensional (3-D) environment as opposed to two-dimensional culture dishes. This 3D culture system is biochemically and physiologically more similar to in vivo tissue, but is technically challenging to maintain because of many factors (e.g. diffusion).
Cell line cross-contamination can be a problem for scientists working with cultured cells. Studies suggest anywhere from 1520% of the time, cells used in experiments have been misidentified or contaminated with another cell line. Problems with cell line cross-contamination have even been detected in lines from the NCI-60 panel, which are used routinely for drug-screening studies. Major cell line repositories, including the American Type Culture Collection (ATCC), the European Collection of Cell Cultures (ECACC) and the German Collection of Microorganisms and Cell Cultures (DSMZ), have received cell line submissions from researchers that were misidentified by them. Such contamination poses a problem for the quality of research produced using cell culture lines, and the major repositories are now authenticating all cell line submissions. ATCC uses short tandem repeat (STR) DNA fingerprinting to authenticate its cell lines.
To address this problem of cell line cross-contamination, researchers are encouraged to authenticate their cell lines at an early passage to establish the identity of the cell line. Authentication should be repeated before freezing cell line stocks, every two months during active culturing and before any publication of research data generated using the cell lines. Many methods are used to identify cell lines, including isoenzyme analysis, human lymphocyte antigen (HLA) typing, chromosomal analysis, karyotyping, morphology and STR analysis.
One significant cell-line cross contaminant is the immortal HeLa cell line.
As cells generally continue to divide in culture, they generally grow to fill the available area or volume. This can generate several issues:
Among the common manipulations carried out on culture cells are media changes, passaging cells, and transfecting cells. These are generally performed using tissue culture methods that rely on aseptic technique. Aseptic technique aims to avoid contamination with bacteria, yeast, or other cell lines. Manipulations are typically carried out in a biosafety hood or laminar flow cabinet to exclude contaminating micro-organisms. Antibiotics (e.g. penicillin and streptomycin) and antifungals (e.g.amphotericin B) can also be added to the growth media.
As cells undergo metabolic processes, acid is produced and the pH decreases. Often, a pH indicator is added to the medium to measure nutrient depletion.
In the case of adherent cultures, the media can be removed directly by aspiration, and then is replaced. Media changes in non-adherent cultures involve centrifuging the culture and resuspending the cells in fresh media.
Passaging (also known as subculture or splitting cells) involves transferring a small number of cells into a new vessel. Cells can be cultured for a longer time if they are split regularly, as it avoids the senescence associated with prolonged high cell density. Suspension cultures are easily passaged with a small amount of culture containing a few cells diluted in a larger volume of fresh media. For adherent cultures, cells first need to be detached; this is commonly done with a mixture of trypsin-EDTA; however, other enzyme mixes are now available for this purpose. A small number of detached cells can then be used to seed a new culture. Some cell cultures, such as RAW cells are mechanically scraped from the surface of their vessel with rubber scrapers.
Another common method for manipulating cells involves the introduction of foreign DNA by transfection. This is often performed to cause cells to express a protein of interest. More recently, the transfection of RNAi constructs have been realized as a convenient mechanism for suppressing the expression of a particular gene/protein. DNA can also be inserted into cells using viruses, in methods referred to as transduction, infection or transformation. Viruses, as parasitic agents, are well suited to introducing DNA into cells, as this is a part of their normal course of reproduction.
Cell lines that originate with humans have been somewhat controversial in bioethics, as they may outlive their parent organism and later be used in the discovery of lucrative medical treatments. In the pioneering decision in this area, the Supreme Court of California held in Moore v. Regents of the University of California that human patients have no property rights in cell lines derived from organs removed with their consent.
It is possible to fuse normal cells with an immortalised cell line. This method is used to produce monoclonal antibodies. In brief, lymphocytes isolated from the spleen (or possibly blood) of an immunised animal are combined with an immortal myeloma cell line (B cell lineage) to produce a hybridoma which has the antibody specificity of the primary lymphocyte and the immortality of the myeloma. Selective growth medium (HA or HAT) is used to select against unfused myeloma cells; primary lymphoctyes die quickly in culture and only the fused cells survive. These are screened for production of the required antibody, generally in pools to start with and then after single cloning.
A cell strain is derived either from a primary culture or a cell line by the selection or cloning of cells having specific properties or characteristics which must be defined. Cell strains are cells that have been adapted to culture but, unlike cell lines, have a finite division potential. Non-immortalized cells stop dividing after 40 to 60 population doublings and, after this, they lose their ability to proliferate (a genetically determined event known as senescence).
Mass culture of animal cell lines is fundamental to the manufacture of viral vaccines and other products of biotechnology.
Biological products produced by recombinant DNA (rDNA) technology in animal cell cultures include enzymes, synthetic hormones, immunobiologicals (monoclonal antibodies, interleukins, lymphokines), and anticancer agents. Although many simpler proteins can be produced using rDNA in bacterial cultures, more complex proteins that are glycosylated (carbohydrate-modified) currently must be made in animal cells. An important example of such a complex protein is the hormone erythropoietin. The cost of growing mammalian cell cultures is high, so research is underway to produce such complex proteins in insect cells or in higher plants, use of single embryonic cell and somatic embryos as a source for direct gene transfer via particle bombardment, transit gene expression and confocal microscopy observation is one of its applications. It also offers to confirm single cell origin of somatic embryos and the asymmetry of the first cell division, which starts the process.
Research in tissue engineering, stem cells and molecular biology primarily involves cultures of cells on flat plastic dishes. This technique is known as two-dimensional (2D) cell culture, and was first developed by Wilhelm Roux who, in 1885, removed a portion of the medullary plate of an embryonic chicken and maintained it in warm saline for several days on a flat glass plate. From the advance of polymer technology arose today’s standard plastic dish for 2D cell culture, commonly known as the Petri dish. Julius Richard Petri, a German bacteriologist, is generally credited with this invention while working as an assistant to Robert Koch. Various researchers today also utilize culturing laboratory flasks, conicals, and even disposable bags like those used in single-use bioreactors.
Aside from Petri dishes, scientists have long been growing cells within biologically derived matrices such as collagen or fibrin, and more recently, on synthetic hydrogels such as polyacrylamide or PEG. They do this in order to elicit phenotypes that are not expressed on conventionally rigid substrates. There is growing interest in controlling matrix stiffness, a concept that has led to discoveries in fields such as:
Cell culture in three dimensions has been touted as “Biology’s New Dimension”. Nevertheless, the practice of cell culture remains based on varying combinations of single or multiple cell structures in 2D. That being said, there is an increase in use of 3D cell cultures in research areas including drug discovery, cancer biology, regenerative medicine and basic life science research. There are a variety of platforms used to facilitate the growth of three-dimensional cellular structures such as nanoparticle facilitated magnetic levitation, gel matrices scaffolds, and hanging drop plates.
3D Cell Culturing by Magnetic Levitation method (MLM) is the application of growing 3D tissue by inducing cells treated with magnetic nanoparticle assemblies in spatially varying magnetic fields using neodymium magnetic drivers and promoting cell to cell interactions by levitating the cells up to the air/liquid interface of a standard petri dish. The magnetic nanoparticle assemblies consist of magnetic iron oxide nanoparticles, gold nanoparticles, and the polymer polylysine. 3D cell culturing is scalable, with the capability for culturing 500 cells to millions of cells or from single dish to high-throughput low volume systems.
Cell culture is a fundamental component of tissue culture and tissue engineering, as it establishes the basics of growing and maintaining cells in vitro. The major application of human cell culture is in stem cell industry, where mesenchymal stem cells can be cultured and cryopreserved for future use. Tissue engineering potentially offers dramatic improvements in low cost medical care for hundreds of thousands of patients annually.
Vaccines for polio, measles, mumps, rubella, and chickenpox are currently made in cell cultures. Due to the H5N1 pandemic threat, research into using cell culture for influenza vaccines is being funded by the United States government. Novel ideas in the field include recombinant DNA-based vaccines, such as one made using human adenovirus (a common cold virus) as a vector, and novel adjuvants.
Plant cell cultures are typically grown as cell suspension cultures in a liquid medium or as callus cultures on a solid medium. The culturing of undifferentiated plant cells and calli requires the proper balance of the plant growth hormones auxin and cytokinin.
Cells derived from Drosophila melanogaster (most prominently, Schneider 2 cells) can be used for experiments which may be hard to do on live flies or larvae, such as biochemical studies or studies using siRNA. Cell lines derived from the army worm Spodoptera frugiperda, including Sf9 and Sf21, and from the cabbage looper Trichoplusia ni, High Five cells, are commonly used for expression of recombinant proteins using baculovirus.
For bacteria and yeasts, small quantities of cells are usually grown on a solid support that contains nutrients embedded in it, usually a gel such as agar, while large-scale cultures are grown with the cells suspended in a nutrient broth.
The culture of viruses requires the culture of cells of mammalian, plant, fungal or bacterial origin as hosts for the growth and replication of the virus. Whole wild type viruses, recombinant viruses or viral products may be generated in cell types other than their natural hosts under the right conditions. Depending on the species of the virus, infection and viral replication may result in host cell lysis and formation of a viral plaque.
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Cell culture – Wikipedia, the free encyclopedia
There are many ways in which human stem cells can be used in research and the clinic. Studies of human embryonic stem cells will yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become the differentiated cells that form the tissues and organs. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A more complete understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. Predictably controlling cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. While recent developments with iPS cells suggest some of the specific factors that may be involved, techniques must be devised to introduce these factors safely into the cells and control the processes that are induced by these factors.
Human stem cells are currently being used to test new drugs. New medications are tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines have a long history of being used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. The availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists must be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. For some cell types and tissues, current knowledge of the signals controlling differentiation falls short of being able to mimic these conditions precisely to generate pure populations of differentiated cells for each drug being tested.
Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including maculardegeneration, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.
Figure 3. Strategies to repair heart muscle with adult stem cells. Click here for larger image.
2008 Terese Winslow
For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stromal cells, transplanted into a damaged heart, can have beneficial effects. Whether these cells can generate heart muscle cells or stimulate the growth of new blood vessels that repopulate the heart tissue, or help via some other mechanism is actively under investigation. For example, injected cells may accomplish repair by secreting growth factors, rather than actually incorporating into the heart. Promising results from animal studies have served as the basis for a small number of exploratory studies in humans (for discussion, see call-out box, “Can Stem Cells Mend a Broken Heart?”). Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells (Figure 3).
Cardiovascular disease (CVD), which includes hypertension, coronary heart disease, stroke, and congestive heart failure, has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic. Nearly 2,600 Americans die of CVD each day, roughly one person every 34 seconds. Given the aging of the population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes, CVD will be a significant health concern well into the 21st century.
Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes). This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells attempting to sustain cardiac output, leading to heart failure, and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.
The use of embryonic and adult-derived stem cells for cardiac repair is an active area of research. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells including mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated as possible sources for regenerating damaged heart tissue. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.
A few small studies have also been carried out in humans, usually in patients who are undergoing open-heart surgery. Several of these have demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries. The mechanism for this repair remains controversial, and the stem cells likely regenerate heart tissue through several pathways. However, the stem cell populations that have been tested in these experiments vary widely, as do the conditions of their purification and application. Although much more research is needed to assess the safety and improve the efficacy of this approach, these preliminary clinical experiments show how stem cells may one day be used to repair damaged heart tissue, thereby reducing the burden of cardiovascular disease.
In people who suffer from type1 diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient’s own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for persons with diabetes.
To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:
Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.
To summarize, stem cells offer exciting promise for future therapies, but significant technical hurdles remain that will only be overcome through years of intensive research.
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What are the potential uses of human stem cells and the …
Findings from animal study have implications for disorders such as chronic obstructive pulmonary disease
IMAGE:Adult lung cells regenerating: Type 1 cells are green. Type 2 cells are red. New Type 2 derived from Type 1 cells are yellow. Nuclei are blue view more
Credit: Jon Epstein, MD & Rajan Jain, MD, Perelman School of Medicine at the University of Pennsylvania, and Christina Barkauskas & Brigid Hogan, Duke University
PHILADELPHIA – A new collaborative study describes a way that lung tissue can regenerate after injury. The team found that lung tissue has more dexterity in repairing tissue than once thought. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Duke University, including co-senior authors Jon Epstein, MD, chair of the department of Cell and Developmental Biology, and Brigid L.M Hogan, Duke Medicine, along with co-first authors Rajan Jain, MD, a cardiologist and instructor in the Department of Medicine and Christina E. Barkauskas, also from Duke, report their findings in Nature Communications
“It’s as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated,” says Epstein. “These aren’t classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate the process in situations where it is insufficient, such as in patients with COPD [chronic obstructive pulmonary disease].”
The two types of airway cells in the alveoli, the gas-exchanging part of the lung, have very different functions, but can morph into each other under the right circumstances, the investigators found. Long, thin Type 1 cells are where gases (oxygen and carbon dioxide) are exchanged – the actual breath. Type 2 cells secrete surfactant, a soapy substance that helps keep airways open. In fact, premature babies need to be treated with surfactant to help them breathe.
The team showed in mouse models that these two types of cells originate from a common precursor stem cell in the embryo. Next, the team used other mouse models in which part of the lung was removed and single cell culture to study the plasticity of cell types during lung regrowth. The team showed that Type 1 cells can give rise to Type 2 cells, and vice-versa.
The Duke team had previously established that Type 2 cells produce surfactant and function as progenitors in adult mice, demonstrating differentiation into gas-exchanging Type 1 cells. The ability of Type I cells to give rise to alternate lineages had not been previously reported.
“We decided to test that hypothesis about Type 1 cells,” says Jain. “We found that Type 1 cells give rise to the Type 2 cells over about three weeks in various models of regeneration. We saw new cells growing back into these new areas of the lung. It’s as if the lung knows it has to grow back and can call into action some Type 1 cells to help in that process.”
This is one of the first studies to show that a specialized cell type that was thought to be at the end of its ability to differentiate can revert to an earlier state under the right conditions. In this case, it was not by using a special formula of transcription factors, but by inducing damage to tell the body to repair itself and that it needs new cells of a certain type to do that.
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One type of airway cell can regenerate another lung cell type