Stem Cell Research

From Stem Cell Research To Genetics, Oxford And Harvard Lead In Data-Sharing Effort

In a move sorely needed in the new and fast growing field of stem cell research and regenerative medicine, more than 50 collaborators at over 30 scientific organizations around the globe have agreed on a common standard that will make possible the consistent description of enormous and very different databases compiled in fields ranging from genetics to stem cell research and therapies.

The new standard provides a way for scientists in widely disparate fields to co-ordinate each other's findings by allowing behind-the-scenes combination of the mountains of data produced by modern, technology driven science.

Skin Cells Turned Into Neural Precusors, Bypassing Stem Cell Stage

New research has converted mouse skin cells directly into cells that become the three main parts of the nervous system. The finding is an extension of a previous study (post)  by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

Importantly, the multiple successes of the direct conversion method could refute the idea that pluripotency is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new research is a substantial advance over the previous work in that it transforms the skin cells into neural precursor cells as opposed to neurons. While neural precursor cells can differentiate into neurons they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes.

Therapeutically Useful Stem Cell Derivatives Need Stability

New research suggests that neural derivatives of human pluripotent stem cells frequently acquire extra material from chromosome 1q, a chromosomal defect that has been associated with some blood cell cancers and pediatric brain tumors with poor clinical outcomes. 

The good news is that the same researchers found that the abnormal neural cells detected were unable to form tumors in mice.  The new cautionary data however does suggests the necessity of additional quality controls to ensure that neural derivatives of human pluripotent stem cells are not genomically unstable, a common characteristic of cancer cells.  The research was accomplished by Natalie Lefort and colleagues, at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, France.

In commentary concerning the research, Neil Harrison, at the University of Sheffield, United Kingdom, noted that while the data raise safety issues relevant for the therapeutic use of these cells, the fact that the same chromosome was affected in all cases suggests that it should be possible to design screening strategies to detect and remove these cells.

Adapted from the Institute for Stem Cell therapy and Exploration of Monogenic Diseases announcement.

 

Researchers Find First Step In Strategy For Parkinson's Disease Induced Pluripotent Stem Cell Replacement Therapy

Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson's disease models.

Now researchers have evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, and have elucidated their therapeutic potential.

"We developed a series of methods to induce human iPSCs to become NPCs, using a feeder-free culture method, and grafted NPCs at different stages of differentiation into the brain of a monkey PD* model," said Jun Takahashi, MD, PhD, of Kyoto University. "We developed a method to evaluate the growth and DA activity of the grafts using magnetic resonance imaging (MRI), positron emission tomography (PET), immunocytochemistry, and behavioral analyses, all of which will be useful in preclinical research."

Stem Cells Show Promise In Delivering Gene Therapy For Hunington's Disease

In a promising approach that might block the disease from advancing, researchers have developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease. Huntington's disease can be managed with medications, but currently there are no treatments for the physical, mental and behavioral decline of its victims.

"We have been able to successfully deliver inhibitory RNA sequences from stem cells directly into neurons, significantly decreasing the synthesis of the abnormal huntingtin protein," said Jan A. Nolta, Director of the UC Davis stem cell program and the UC Davis Institute for Regenerative Cures.

Human Pluripotent Stem Cells Induced To Become High Purity Vascular Smooth Muscle

Using human pluripotent stem cells, researchers have discovered a method for creating high purity vascular smooth muscle. 

Although blood and cardiac cells from human pluripotent stem cells have been created before, this is the first time that all the major types of vascular smooth muscle cells have been developed in an easily scalable manner.

In the UK, one in three of all deaths is due to cardiovascular disease. The vast majority of these are caused by atherosclerosis, a ‘furring up’ and blockage of blood vessels. For patients who are unsuitable for conventional stenting or bypass treatment, one option in the future may be to grow new blood vessels to bypass their own blocked vessels.

Video: Lawrence Goldstein -- Evidence-based Development of Stem Cell Therapies

As we move forward in clinical trials for autologous and allogeneic stem cell therapies, recognition of what we don't know and what we do is both critical and constantly changing. The integration of this expanding stem cell knowledge with the parallel expansion of our knowledge of the biochemestry and molecular biology of the human body will hopefully produce continually improving therapies. However, the acquisition of knowledge and understanding is not linear. Research in therapies can get ahead of our understanding of disease process and have. This video is a reality check on what we know of neurodegenerative disease and potential therapy as of October 2011. It is well worth watching.

Taking place at the World Stem Cell Summit, this talk is about 37 minutes long. With an emphasis on Alzheimer's disease, Dr. Goldstein does a truly excellent job of pointing out the difficulty of understanding

New Research Sheds Light On Early Embryonic Stem Cell Development Through First Time Birth Of Chimeric Monkeys From Stem Cells Taken From Two Separate Embryos

Conducted to gain a better understanding of the differences between natural stem cells residing in early embryos and their cultured embryonic stem cell  counterparts, the new work also determined that stem cell functions and abilities differ between primates and rodents.

The first cels studied were those that were totipotent – cells from the early embryo that have the ability to divide and produce all of the differentiated cells in the placenta and the body of an organism. These were compared with pluripotent cells – cells derived from the later stage embryo that have the ability to produce all body parts except those necessary for reproduction.

New Research Finds Induced Pluripotent Stem Cells Match Embryonic Stem Cells In Modeling Human Disease

Induced Pluripotent Stem Cells (iPS cells) can mirror the defining defects of a genetic condition — in this instance, Marfan syndrome — as well as embryonic stem cells.

An immediate implication is that iPS cells could be used to examine the molecular aspects of Marfan on a personalized basis. Embryonic stem cells, on the other hand, can’t do this because their genetic contents are those of the donated embryo, not the patient’s.

Tweaking Elements In Reprogramming Of Adult Cells Can Greatly Affect The Quality Of The Resulting Induced Pluripotent Stem Cells

Since the creation of the first iPS cells in 2006, researchers using various reprogramming techniques have reported a broad spectrum of efficiency rates and quality of resulting iPS cells.

Although researchers have shown iPS cells can fulfill all developmental tests applied to ES cells, recent reports have identified molecular differences that can influence their developmental potential and render them less-than-equivalent partners to ES cells. These inconsistencies have tarnished the promise of iPS cells, dampened enthusiasm, and fueled speculation that they may never be used therapeutically.

Now research has shown that tweaking the levels of factors used during the reprogramming of adult cells into induced pluriopotent stem (iPS) cells greatly affects the quality of the resulting iPS cells.

"This conclusion is something that I think is very surprising or unexpected—that the levels of these reprogramming factors determine the quality of the iPS cells," said Whitehead Founding Member and pioneer stem cell researcher Rudolf Jaenisch. "We never thought they'd make a difference, but they do."

Autism And Induced Pluripotent Stem Cells

Dr. Ricardo Dolmetsch, associate professor of neurobiology, Stanford University, has generated stem cells from the cells of children with autism. This is a straight forward, brief interview which talks to the question of stem cells and autism. During the interview Dolmetsch gives a cogent explanation of the possibilities for Induced Pluripotent Stem Cells in disease and therapeutic research.

 

 

Stem Cell Research Advanced As Key To Cell Specialization Is Discovered

New research has uncovered a mechanism that governs how cells become specialized during development.

In an attempt to determine how a fertilized egg gives rise to many different cells in the body, researchers studied cell differentiation in the fruit fly, Drosophila Melanogaster. They found that cell specialization depends on a pair of proteins that act as super regulators of proteins that were already known—one super-regulating protein encouraging a cell to differentiate and the other trying to hold back the process.

In particular, researchers studied Helix-Loop-Helix proteins, “master-regulating” proteins that were known to play a role in the differentiation of fruit fly cells such as muscle, fat and nervous-system cells. By examining eye

Rejuvinated Induced Pluripotent Stem Cells Produced From Cells Of Elderly Donors, Some Over 100 Years Old

Until now, research results demonstrated that senescence (the final stage of cellular aging) was an obstacle blocking the use of stromal cells, ones that had been induced into pluripotent, embryonic-like stem cells, for therapeutic applications in elderly patients.

The researchers successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.

Programming Stem Cells to Home to Specific Tissues Should Enable More Effective Cell-based Therapies

The inability to target stem cells to tissues of interest poses a significant barrier to effective cell therapy.

New research has developed a platform approach to chemically incorporate homing receptors onto the surface of stem cells. This approach has the potential to improve the efficacy of many types of stem cell therapies by increasing the concentrations of cells at target locations in the body.

To accomplish this, researchers engineered the surface of cells to include receptors that act as a homing device.

New Research Shows Stem Cell Reprogramming Technique Is Safer Than Previously Thought

Researchers have feared that dangerous mutations within induced pluripotent stem cells might be caused by current reprogramming techniques. A sophisticated new analysis of stem cells’ DNA finds that such fears may be unwarranted.

The induced pluripotent stem cell (iPSC) technique requires the insertion  of four special genes into an ordinary adult non-stem cell. The four genes cause the cell to revert to a state like that of embryonic stem cell. In principle, iPSCs may be used to repair diseased or damaged tissues, and because they are made from a patient’s own cells, they shouldn’t provoke an immune reaction. But recent studies have found unacceptably high levels of mutations in iPSCs derived from adult human cells. That has led to widespread suspicion that the reprogramming process is largely to blame.

New Gene Therapy Utilizing Induced Pluripotent Stem Cells Corrects Mutation In Patient's Stem Cells

Researchers targeted a gene mutation responsible for both cirrhotic liver disease and lung emphysema and were able to correct the sequence of a genome, remove all exogenous DNA, and show that the corrected gene worked normally.

The researchers used human induced pluripotent stem cells (hIPSCs) because, once reprogrammed, these cells can be converted into a wide range of tissues. If cells from a patient with a gene defect can be corrected, scientists believe that when reintroduced into the patient they could treat the effects of the mutation causing the disease.

Induced Pluripotent Stem Cell State Much Easier To Achieve In New Reprogramming Approach

Researchers have found a new, more efficient, technique to reprogram human adult cells, such as skin cells, into induced pluripotent stem cells.

Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors the new research seems to have brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development.

Video: The Fundamentals Of Stem Cell Clinical Trials For Spinal Cord Repair

This talk is by Professor Alan Mackay-Sim of Griffith University, Brisbane Australia. Mackay-Sim is the Director as well as Chief Investigator for the Australian National Center for Stem Cell Research. His talk is on Cell Transplantation for Spinal Cord Repair, with reference to the methodology of clinical trials. He also addresses the Geron Corp. clinical trial currently under way as well as a clinical trial on spinal cord repair that he has undertaken.

The presentation is directed at a lay audience.

 

 

 

Cedars-Sinai opens new Induced Pluripotent Stem Cell Core Production Facility

The new facility will use the latest technology to generate induced pluripotent stem cells (iPS cells) from a patient's skin scraping. Such induced pluripotent stem cells can be replicated indefinitely and have biological properties similar to embryonic stem cells.   These “blank slate” cells can then be turned into any kind of differentiated cell, such as a brain cell or an eye cell or a liver cell.

“Opening the Cedars-Sinai Stem Cell Core Facility underscores what an exciting time this is in regenerative medicine," said Shlomo Melmed, MD, senior vice president of academic affairs and dean of the faculty at Cedars-Sinai.  “It also is an example of Cedars-Sinai’s deep commitment to the scientific research that will be translated into tomorrow’s leading-edge treatments.”

Dr. Gary Steinberg: Video Presentation Of Stem Cell Therapy For Stroke

Gary Steinberg, Stanford University, is a pioneer in stem cell research for stroke. This is a CIRM presentation that took place August 19 of 2010. Steinberg presents the subject broadly, touching on most of what has taken place and suggesting ideas of where we're headed in the stem cell therapy for stroke arena.

 

First Full Measurement and Comparison of Proteins Made By Embryonic and Induced Pluripotent Stem Cells

In a study of four embryonic stem cells and four IPS cells, proteins turned out to be 99 percent similar according to  Joshua Coon, associate professor of chemistry and biomolecular chemistry at the University of Wisconsin Madison.

Proteins are complex molecules made by cells for innumerable structural and chemical purposes, and the new study measured more than 6,000 individual proteins using highly accurate mass spectrometry, a technique that measures mass as the first step of identifying proteins.

"This study is the first comprehensive comparison of proteins in the two stem cell types," said Doug Phanstiel, who is now at Stanford University.

Stem Cells Induced To Develop Into Specific Types Of Cells Solely By Controlling Their Shape

Stem cells are used in tissue engineering to repair or re-grow damaged body tissues. This new research utilized human bone marrow stromal cells, adult stem cells that can be isolated from bone marrow and can differentiate into bone, fat or cartilage cells, depending...

"Depending on what?" is one of the key questions in tissue engineering. How do you ensure that the stem cells turn into the type you need? Chemical cues have been known to work in cases where researchers have identified the proper additives—a hormone in the case of bone cells. Other research has suggested that cell differentiation on flat surfaces can be controlled by patterning the surface to restrict the locations where growing cells can attach themselves.

The Basics And Future Of Stem Cell Research: Amander Clark, UCLA

Amander Clark's laboratory uses embryonic stem cells as a model to study molecular events critical for human embryo development, with a special emphasis on the human germ line. She and her research team currently lead the effort at UCLA to generate new embryonic stem cell lines, with a major goal being the generation of clinic-grade lines for use in future therapeutics.

The video is Dr. Clark's UCLA Life Sciences Public Lecture delivered on March 16, 2011, and titled, "The Next Frontier in Stem Cell Research." It is an excellent summary of where we are and where were going.

 

Researchers Discover Method Of Removing Potential Tumor-Causing Stem Cells From Cells Developed For Use In Medical Treatments

Effective tricks for separating stem cells from other types are essential for many emerging medical treatments. These treatment approaches begin with researchers inducing stem cells to take specific forms, or differentiate, for instance into nerve cells. These differentiated cells might then be used to repair a spinal cord injury. Other cells might enable a diabetic's body to produce adequate insulin.

A key problem is that in the differentiation process, at least some stem cells inevitably remain in their undifferentiated, or pluripotent, state. These cells can grow to form tumors in patients if injected along with differentiated cells, a concern that has already led the US Food and Drug Administration (FDA) to delay clinical trials for promising stem cell-based therapies.

Stem Cell Pluripotency Tied To Key Protein

Embryonic stem cells (ES cells) and induced-pluripotent stem cells (iPS cells) promise a new era of cell-based treatments for a wide range of conditions and diseases. They do this through their capacity to differentiate into any other type of cell.

Cultivating such cells has relied on the use of so-called "feeder" cells to maintain pluripotency in cell culture conditions. Feeder cells keep stem cells in their undifferentiated state by releasing nutrients into the culture medium. But they also have the potential to introduce contamination which, in humans, can lead to serious health risks.

Induced Pluripotent Stem Cells: Human Skin Cells Induced To Become Nuerons

In late May we posted about Stanford University research wherein human skin cells were converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins.

In this recent research, Dr. Sheng Ding used two genes and a microRNA to convert a skin sample from a 55-year-old woman directly into brain cells. (MicroRNAs are tiny strands of genetic material that regulate almost every process in every cell of the body.) The cells created by Dr. Ding’s experiments exchanged the electrical impulses necessary for brain cells to communicate things such as thoughts and emotions. Using microRNA to reprogram cells is a safer and more efficient way than using the more common gene-modification approach. In ensuing experiments, Dr. Ding hopes to rely only on microRNAs and pharmaceutical compounds to convert skin cells to brain cells, which should lead to more efficient generation of cells for testing and regenerative purposes.

Researchers Improve Method Of Producing Induced Pluripotent Stem Cells

iPS cells are currently produced by introducing four defined genes to an adult cell. The genes reprogram the adult cell into a stem cell which can differentiate into many different types of cells. Typically, the four genes introduced are Oct4, Sox2, Klf4 and c-Myc, a combination known as OSKM.

Now researchers have found that fusing two proteins – stem cell regulator (Oct4) and a fragment of a muscle cell inducer (MyoD) – they can "power up" the stem cell regulator, dramatically improving the efficiency and purity of reprogrammed iPS cells.

Cells Derived From Pluripotent Stem Cells Shown As Developmentally Immature

Three types of cells derived from human embryonic stem cells and induced pluripotent stem cells are similar to each other, but are much more developmentally immature than previously thought when compared to those same cell types taken directly from human tissue.

New research involving a two year study has found the progeny of the human embryonic stem cells and induced pluripotent stem cells (iPS) resemble cells found within the first two months of fetal development rather than anything later, a result that could have implications both clinically and for disease modeling according to William Lowry, assistant professor of molecular, cell and developmental biology with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Shinya Yamanaka On Induced Pluripotent Stem Cells

Recent talk by Shinya Yamanaka, the father of induced pluripotent stem cells and the first to induce a human skin cell to become an embryonic-like stem cell. He speaks of his philosophy and experience to date with understanding induced pluripotent stem cells (iPS cells), their differences from embryonic stem cells, and the future of iPS cells as they evolve into disease analysis and stem cell therapy.  This took place at the University of San Francisco.

 

Video: Edward Morrisey Explaining Induced Pluripotent Stem Cells Using MicroRNA Expression

iPSCs are typically generated from adult non-reproductive cells by expressing four different genes called transcription factors.  The generation of iPSCs was first reported in 2006 by Shinya Yamanaka, and multiple groups have since reported the ability to generate these cells using some variations on the same four transcription factors. Since then researchers have been searching for ways to reprogram somatic cells without using viral transcription factors. See Sheng Ding and Yanik, MIT.

The promise of this line of research is to one day efficiently generate patient-specific stem cells in order to study human disease as well as create a cellular "storehouse" to regenerate a person's own cells, for example heart or liver cells. Despite this promise, generation of iPSCs is hampered by low efficiency, especially when using human cells.

“This is the first time we've been able to make induced pluripotent stem cells without the four transcription factors and increase the efficiency by 100-fold,” said Edward Morrisey, PhD, professor Departments of Medicine and Cell and Developmental Biology and Scientific Director at the Penn Institute for Regenerative Medicine. "It's a game changer," he added.

Stem Cell Therapy May Be Freed Of Teratoma Threat By New Research

Scientists are seemingly approaching a day when they will be able to make nearly any type of tissue from human embryonic stem cells. You need nerves or pancreas, bone or skin? With the right combination of growth factors, skill and patience, a laboratory tissue culture dish promises to yield therapeutic wonders. But within these batches of newly generated cells lurks a big potential problem: Any remaining embryonic stem cells - those that haven't differentiated into the desired tissue - can go on to become dangerous tumors called teratomas when transplanted into patients.

Teratomas are the Frankensteins of the tumor world - a hodgepodge of tissues like teeth, hair and bone. They owe their remarkable composition to the fact that the cells from which they arise early in development are pluripotent. In fact, the ability to form teratomas in animals is a defining feature of true pluripotent cells.
      
But the very feature that confirms a cell's pluripotency also makes it potentially dangerous to use therapeutically. Researchers at the Stanford School of Medicine decided to try to develop an antibody that would recognize and bind to only pluripotent cells and enable their removal from a mixture of cells. Although a few such antibodies already existed, they were not specific enough on their own to completely weed out the tumor-causing cells.

"Inducing Induced Pluripotent Stem Cells (iPSCs) To Escape The Dish:" Strategies To Advance Toward Stem Cell Therapies

New research has produced a roadmap for finding solutions to the problems identified with iPSCs.

iPSCs were first produced in 2006 from mouse cells and in 2007 from human cells. They have many of the same regenerative properties as human embryonic stem cells, but they are derived in a lab from adult cells, such as skin cells, by inducing or forcing them to express specific genes that are normally dormant in that type of cell. In theory, a person's skin cells could be induced to make neurons that produce the neurotransmitter dopamine, for example, and be delivered to brain regions where it is lacking in patients with Parkinson's disease. Similarly, cells could be induced to regenerate heart muscle and blood vessels after a heart attack, or neurons following a spinal cord injury.

Stem Cell Therapies For ALS, or Lou Gehrig’s disease: The Problem And New Clinical Trials

Two of our Stem Cell Sector companies, Neuralstem (CUR) and Brainstorm Cell Therapeutics (BCLI.OB) are in clinical trials with stem cell therapies for Amyotrophic lateral sclerosis (ALS), also known as Lou Gherig's disease. Neuralstem (CUR), market cap $60M, began its ALS trial in 2008 in the United States.

BrainStorm, market cap $57M, is the first company to receive approval from the Israeli Ministry of Health (MOH) for a differentiated stem cell therapy and approval of its Phase I/II clinical trial utilizing its proprietary NurOwn™ treatment for patients with Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's Disease. BrainStorm's trial effectively began in Isreal on June 6,2011.

On July 19, 2011, BrainStorm announced it will partner with UMass Medical School and its chair of neurology, Robert H. Brown Jr., DPhil, MD, in anticipation of applying for FDA approval to begin amyotrophic lateral sclerosis (ALS) human clinical trials in the United States. The trial, which will be conducted at Massachusetts General Hospital, will investigate the use of the company’s NurOwn treatment for ALS.

We've included a video talk by Fred Gage of the Salk Institute on the subject of how ALS works in the body.

Can Induced Pluripotent Stem Cells from a Patients' Own Kidney Cells Cure Kidney Disease?

New research indicates that patients' own kidney cells can be gathered and reprogrammed into Induced Pluripotent Stem Cells.

Two studies were recently published in the Journal of the American Society Nephrology (JASN).

In the first study, Sharon Ricardo, PhD (Monash University, in Clayton, Australia) and her colleagues took cells from an individual's kidney and coaxed them to become progenitor cells, allowing the immature cells to form any type in the kidney. Specifically, they inserted several key reprogramming genes into the renal cells that made them capable of forming other cells.

Technique Boosts Efficiency Of Blood Cell Production From Human Stem Cells

An improved technique for generating large numbers of blood cells from a patient's own cells has been developed at the Salk Institute for Biological Studies. Researchers suggest the new technique will be immediately useful in further stem cell studies.  When perfected, it could be used in stem cell therapies for a wide variety of conditions. Other techniques are also being developed by other researchers, including the University of Glasgow which we posted about recently.

"There are further improvements that we need to make, but this takes us a significant step closer to the ultimate goal, which is to be able to take ordinary cells from a patient, induce them to become stem cells, and then use those stem cells to rebuild lost or diseased tissues, for example the patient's bone marrow," said Inder M. Verma, PhD, Professor of Molecular Biology at the Salk Institute Laboratory of Genetics.

Stem Cell Research, Regenerative Medicine and Therapies: The Macro

Blogs, being new themselves, emphasize the currency of posts as paramount. We disagree. History is important. It is more important in some fields than in others. This video, made in 2006, is more relevant today than it was then. Not surprising given the short overall history of regenerative medicine and stem cell research. This is a marvelous macro summary of regenerative medicine. Taken in the context of subsequent events that include even more dramatically increasing health care costs, a national health care debate that has come to the fore, the continuing arguments against embryonic stem cell research, and the patchwork attempt at a national healthcare solution, this is a very worthwhile 18 minute investment. We should add that In those specific therapeutic arenas emphasized in Alan Russell’s talk, only progress has ensued since.

Dr. Alan Russell (PhD in Biological Chemistry, 1987, Imperial College of Science and Technology, University of London) is a Distinguished University Professor of Surgery and the Founding Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

Stem Cell Versatility Controlled By Protein Alliances And Competition

Like people with a big choice to make, stem cells have a process to "decide" whether to transform into a specific cell type or to stay flexible, a state that biologists call "pluripotency.

New research has shown that different proteins called transcription factors compete and cooperate in stem cells to produce complex bindings along crucial sequences of DNA. This game of molecular "capture the flag," played in teams and amid shifting alliances, appears to be a necessary part of what determines whether stem cells retain their pluripotency and whether specialized, or differentiated, cells can regain it.

Researchers Discover Key Molecule for Stem Cell Pluripotency

Researchers have shown that pluripotency in  mouse embryonic fibroblasts (MEFs) is directly associated with the cell-adhesion molecule E-cadherin. If E-cadherin is absent, the stem cells lose their pluripotency.

What happens when somatic cells that normally neither have E-cadherin nor are pluripotent are reprogrammed into a pluripotent stem cell state was also investigated. In this reprogramming technique, somatic cells are converted into induced pluripotent stem cells (iPSCs).

Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch found that in contrast to the original cells, the new pluripotent cells derived from mouse connective tissue contained E-cadherin. “Thus, we have double proof that E-cadherin is directly associated with stem-cell pluripotency. E-Cadherin is necessary for maintaining pluripotent stem cells and also for inducing the pluripotent state in the reprogramming of somatic cells,” said Dr. Daniel Besser. “If E-cadherin is absent, somatic cells cannot be reprogrammed into viable pluripotent cells.” In an additional finding, Besser noted that E-Cadherin can replace OCT 4, one of the signaling molecules until now considered indispensable for reprogramming.

Next, the MDC researchers want to find out to what extent E-cadherin also regulates human embryonic stem cells. “Understanding the molecular relationships is essential for using human somatic cells to develop stem cell therapy for diseases such as heart attack, Alzheimer’s or Parkinson’s disease or diabetes,” Dr. Besser said.

Adapted from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch announcement.

Human Skin Cells Turned Directly Into Neurons, Skipping Induced Pluripotent Stem Cell Stage

Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins according to new research.

The new approach may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells — seemingly on the basis of the proteins used to render them pluripotent.

The new research parallels that of the same Stanford University School of Medicine group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly.

Induced Pluripotent Stem Cell Therapies Could Encounter Immune Rejection Problems

Researchers have reported the first clear evidence of immune system rejection with cells derived from autologous iPSCs (Induced Pluripotent Stem Cells) that can be differentiated into a wide variety of cell types. Basically the process involves inducing other autologous cells, such as skin cells, into an embryonic-like state, from which they are then again induced to become whatever type of cell is needed.

Heart Cells Derived from Stem Cells Used to Study Heart Diseases

New research is using Induced Pluripotent Stem Cell (iPSC) technology to make heart cells from skin cells specifically to study certain genetic mechanisms of heart diseases. The goal is to offer a cell model allowing researchers to study disease mechanisms, and new treatments and therapies for genetically based heart diseases such as inherited arrhythmias.

The research group, led by Drs. Craig January and Tim Kamp, professors of medicine at the University of Wisconsin School of Medicine and Public Health, is among the first to use research of this kind specifically for certain genetically based heart diseases. Their results show that the study of heart cells derived from stem cells offer a powerful tool for understanding and treating genetically based heart disease.

"By using patient-derived cardiomyocytes, or heart cells, to isolate a disease process outside of the body," said Dr. January, "we are able to gain information about how that gene affects the heart, and how it may respond to treatments and therapies, without having to greatly impact the affected patient. We can mimic the disease process in vitro, reproduce and observe the cells, and also test them with different medications to see how they will actually respond in the heart."

Adapted from the Univirsity of Wisconsin School of Medicine and Public Health announcement.

 

Researchers Validate Important Role of iPSCs in Regenerative Medicine

Researchers have demonstrated that induced pluripotent stem cells (iPSCs) can differentiate into definitive endoderm cells, in vitro, with similar functional potential when compared to embryonic stem cells (ESCs), despite minor molecular differences between the two cell types.

These findings are particularly important given growing controversy in the scientific literature about whether subtle differences between iPSCs and ESCs should dampen enthusiasm for iPSCs to serve as an alternative source of differentiated precursor cells for various tissues, such as the liver, lung or blood. The new work provides compelling evidence that iPSCs have potential in regenerative medicine as an investigational tool for the development of treatments against diseases that affect endodermal-derived organs, such as cirrhosis, diabetes, cystic fibrosis and emphysema.

Stanford Creates First PhD Program In Stem Cell Science

In a rare step that acknowledges the growing importance of stem cell research in the realm of biomedical science, Stanford University has created a new doctoral program in Stem Cell Science.

Stanford officials believe the new program that might lead to new stem cell therapies is the first stem cell science PhD program in the nation and, perhaps, the world. The new doctoral program in stem cell biology and regenerative medicine is also the first interdisciplinary doctoral program created by the School of Medicine in recent years.

“Stem cell biology is a distinct discipline that requires unique skills and includes a scope of knowledge and a skill set that is not covered by other disciplines,” said Renee Reijo Pera, PhD, professor of obstetrics and gynecology and director of the new PhD program.

Embryonic Stem Cell Therapy, iPS Cell Therapy And Regenerative Medicine From The Perspecitve Of a World Renowned Transplant Surgeon

A fine broad perspective on the hope for Regenerative Medicine and Stem Cell Therapies is presented by Dr. Susan Lim in this video.

Susan Lim established her reputation as a surgeon in 1990 after performing Singapore's (and southeast Asia's) first successful liver transplant. She has gone on to further pioneer in the field of general surgery, two new surgical technologies for Singapore, the mammotome minimally invasive breast biopsy and robotic surgery for the private sector. She founded and is chair and CEO of Centre for Robotic Surgery and spearheaded the Robotic General Surgery Program for Singapore.

 

New Test for "Pluripotent" Stem Cells Developed

A research team has created a quality control diagnostic test that will make it easier for researchers to determine whether their cell lines are normal pluripotent cells. The new test, called "PluriTest," meets the need for a cost-effective, accurate, animal-free alternative to the teratoma assay for assessing pluripotency.

"Many scientists are unhappy with the current gold standard for testing for pluripotency, called the teratoma assay," said Scripps Research molecular biologist Jeanne Loring. "The teratoma assay requires animal testing and a time span of six to eight weeks before scientists can prove that they have a pluripotent stem cell line. In addition, this method is technically challenging and difficult to standardize."

Induced Pluripotent Stem Cells From Blood Cells May Expose Cancer At Earliest Stage

By coaxing healthy and diseased human bone marrow to become embryonic-like stem cells researchers have laid the groundwork for observing the onset of the blood cancer leukemia in the laboratory dish.

"This is the first successful reprogramming of blood cells obtained from a patient with leukemia," said Igor Slukvin, University of Wisconsin-Madison stem cell researcher, who directed the research aimed at generating all-purpose stem cells from bone marrow and umbilical cord blood. "We were able to turn the diseased cells back into pluripotent stem cells. This is important because it provides a new model for the study of cancer cells."

Researchers used banked healthy and diseased bone marrow and cord blood. They employed a technique developed in 2009 by Wisconsin stem cell pioneer James Thomson that sidesteps the problems posed by the genes and viral vectors used to induce mature cells to regress to a stem cell state.

The new research points out that the reprogramming blood cells to become induced stem cells is many times more efficient than the reprogramming of skin cells, the first mature cells to be guided back to an embryonic stem cell-like state.

Rare disease reveals new path for creating stem cells

By mimicking a rare genetic disorder in a dish, researchers have found they can rewind the internal clock of a mature cell and drive it back into an adult stem-cell stage. This new "stem cell" can then branch out into a variety of differentiated cell types, both in culture and in animal models.

Fibrodysplasia Ossificans Progressiva (FOP), which affect fewer than 1,000 people worldwide, is a horrific genetic disease in which acute inflammation causes soft tissue to morph into cartilage and bone. Over the course of a few decades, patients gradually become thoroughly ossified, as though parts of their body have turned to stone. There is no cure or treatment.

Damian Medici, an instructor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, found that, unlike normal skeletal tissue, the pathological cartilage and bone cells from these patients contained biomarkers specific for endothelial cells—cells that line the interior of blood vessels. This led him to question whether or not the cartilage and bone growing in soft tissues of FOP patients had an endothelial origin.

Medici and his colleagues transferred the mutated gene that causes FOP into normal endothelial cells. Unexpectedly, the endothelial cells converted into a cell type nearly identical to what are called mesenchymal stem cells, or adult stem cells that can differentiate into bone, cartilage, muscle, fat, and even nerve cells.

Researchers Find Solution to Cell Death Problem Vexing Stem Cell Research

Human pluripotent stem (hPS) cells can generate any given cell type in the adult human body, which is why they are of interest to stem cell scientists working on finding stem cell therapies for spinal cord injuries, Parkinson's disease, burns, heart disease, diabetes, arthritis, and other ailments.

Before hPS cell technologies can be translated into clinical applications, however, some obstacles must first be overcome.

One such obstacle frustrating stem cell researchers is “cell death” that the major types of hPS cells, including human embryonic stem cells and human induced pluripotent stem cells, mysteriously undergo when cultured as single cells, rendering them less suitable for research.

Researchers at the University of California, Riverside now show that a molecular motor, called “nonmuscle myosin II” (NMII), which exists naturally inside each hPS cell and controls various cellular functions, triggers the death of hPS cells when they are broken down to single cells.

While many details of how exactly NMII works remain unknown, a wide consensus among researchers is that NMII induces a contraction of the main internal components of the cells, eventually resulting in cell death.

RNA Offers A Safer Way To Reprogram Adult Cells Into Induced Pluripotent Stem Cells

Techniques now used to transform cells into induced pluripotent stem cells (iPS cells) pose some serious safety hazards. To deliver the genes necessary to reprogram cells to a pluripotent state, scientists use viruses carrying DNA, which then becomes integrated into the cell's own DNA. But this so-called DNA-based reprogramming carries the risk of disrupting the cell's genome and leading it to become cancerous.

Now, for the first time, MIT researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell's protein-making machinery. This method could prove much safer than DNA-based reprogramming, say the researchers, Associate Professor of Electrical and Biological Engineering Mehmet Fatih Yanik and electrical engineering graduate student Matthew Angel.

In recent years, scientists have shown that they can reprogram human skin cells to an immature state that allows the cells to become any type of cell. This ability, known as pluripotency, holds the promise of treating diseases such as diabetes and Parkinson's disease by transforming the patients' own cells into replacements for the nonfunctioning tissue. With the problems with using viruses well known, demonstrating that the genes necessary for reprogramming can be delivered with RNA is a significant achievement.

"Before this, nobody had a way to transfect cells multiple times with protein-encoding RNA," says Yanik. (Transfection is the process of introducing DNA or RNA into a cell without using viruses to deliver them.) So far, the researchers cannot claim to have reprogrammed the cells into a pluripotent state. To prove that, they will need to grow the cells for a longer period of time and study their ability to develop into other cell types — a process now underway in their lab.

New Type Of Human Stem Cell Easier To Manipulate

Researchers have a developed a new type of human pluripotent stem cell that can be manipulated more readily than currently available stem cells. The new cells can be used to create better cellular models of disease processes and eventually may permit repair of disease-associated gene mutations.

"It has been fairly easy to manipulate stem cells from mice, but this has not been the case for traditional human stem cells," explains Niels Geijsen, PhD, at the Massachusetts General Hospital Center for Regenerative Medicine.  "We had previously found that the growth factors in which mouse stem cells are derived define what those cells can do, and now we've applied those findings to human stem cells."

The first mammalian embryonic stem cells (ESCs) were derived from mice and have proven very useful for studying gene function and the impact of changes to individual genes. But techniques used in these studies to introduce a different version of a single gene or inactivate a particular gene were ineffective in human ESCs. In addition, human ESCs proliferate much more slowly than do cells derived from mice and grow in flat, two-dimensional colonies, while mouse ESCs form tight, three-dimensional colonies. It is been extremely difficult to propagate human ESCs from a single cell, which prevents the creation of genetically manipulated human embryonic stem cell lines.