Stem Cell Research

Brain Stem Cell Development Prompted By Common Diabetes Drug

Researchers have found that metformin, a drug commonly used to treat Type II diabetes, can help trigger the pathway used to instruct stem cells in the brain to become neural (nerve) cells. Brain stem cells and the neural cells they generate play a role in the repair of the injured or degenerating brain.

“If you could take stem cells that normally reside in our brains and somehow use drugs to recruit them into becoming appropriate neural cell types," Dr. Freda Miller, Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto, "then you may be able to promote repair and recovery in at least some of the many brain disorders and injuries for which we currently have no treatment."

Video: Researchers Watch In Real Time As Stem Cells Regenerate Tissue

Using a sophisticated imaging technique, researchers also demonstrated that mice lacking a certain type of cell do not regrow hair. The same technique could shed light on how stem cells interact with other cells and trigger repairs in a variety of other organs, including lung and heart tissue.

“This tells us a lot about how the tissue regeneration process works,” said Valentina Greco, assistant professor of genetics and of dermatology at the Yale Stem Cell Center.

 

Greco and her team focused on stem cell behavior in the hair follicle of the mouse. The accessibility of the hair follicle allowed real-time and non-invasive imaging through a technology called 2-photon intravital microscopy.

Mechanism That Maintains Stem Cell Readiness Identified

 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow according to new research. The family of proteins investigated in the research could help open a new field of biology integrating immunology with stem cell and cancer research.

“Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers,” said Dr. Chengcheng “Alec” Zhang, assistant professor in UT Southwestern’s departments of physiology and developmental biology. “Our research identified a protein receptor on cancer cells called a classical immune inhibitory receptor that inhibits differentiation. Knowing the identity of this protein should facilitate the development of new drugs to treat cancers.”

Researchers Correct Huntington's Disease Mutation in Induced Pluripotent Stem Cells

Researchers have corrected the genetic mutation responsible for Huntington’s disease using human induced pluripotent stem (iPS) cells produced from a patient suffering from the neurodegenerative disorder. The diseased iPS cells were genetically corrected and used to generate neural stem cells. These mutation-free cells were then transplanted into a mouse model of Huntington's where they are generating normal neurons in the area of the brain affected by the disease.

“We believe the ability to make patient-specific, genetically corrected iPSCs from Huntington's patients is a critical step for the eventual use of these cells in cell replacement therapy,” said Buck Institute faculty member Lisa Ellerby, PhD. Here, “the genetic correction reversed the signs of disease in these cells – the neural stem cells were no longer susceptible to cell death and the function of their mitochondria was normal.”

Autologous Stem Cells, Pig Kidney Shells As Scaffolds, Regenerative Medicine, And The Possibility Of Patient Specific Manufactured Organs

The science of regenerative medicine has already had success engineering skin, cartilage, bladders, urine tubes, trachea and blood vessels in the lab that were successfully implanted in patients. These structures were able to receive oxygen and nutrients from nearby vascularized tissues until they developed their own blood vessel supply.

Here, researchers successfully used pig kidneys to make “scaffolds” or support structures that could potentially one day be used to build new kidneys for human patients. The idea is to remove all animal cells – leaving only the organ structure or “skeleton.” A patient’s own cells would then be placed on the scaffold, making an organ that the patient theoretically would not reject.

The “holy grail” of regenerative medicine is to engineer complex organs such as the kidney, liver, heart and pancreas. These organs are very dense with cells and must have their own oxygen supply to survive. This need for a scaffold with a full vasculature is why scientists are exploring the possibility of removing cells from donor organs and replacing them with a patient’s own cells, thereby effectively using the donor organ as a scaffold.

“It is important to identify new sources of transplantable organs because of the critical shortage of donor organs,” said lead author Giuseppe Orlando, M.D., an instructor in surgery and regenerative medicine at Wake Forest Baptist Medical Center. “These kidneys maintain their innate three-dimensional architecture, as well as their vascular system, and may represent the ideal platform for kidney engineering.”

Master Molecule May Improve Stem Cell Treatment for Heart Attacks

Researchers have discovered that a single protein molecule may hold the key to turning cardiac stem cells into blood vessels or muscle tissue.

The team reported that tinkering with a protein molecule called p190RhoGAP shaped the development of cardiac stem cells, prodding them to become the building blocks for either blood vessels or heart muscle. The team members said that by altering levels of this protein, they were able to affect the future of these stem cells.

“In biology, finding a central regulator like this is like finding a pot of gold,” said Andre Levchenko, a biomedical engineering professor and member of the Johns Hopkins Institute for Cell Engineering.

In Step Toward Alzheimer's Therapy, Neural Stem Cells Induced From Transfer Of Single Gene Form Interconnected, Functional Network Of Brain Cells

This research comes at a time of renewed focus on Alzheimer's disease which currently afflicts 5.4 million people in the United States alone—a figure expected to nearly triple by 2050. There are no approved medications to prevent or reverse the progression of this debilitating disease.

A single gene, Sox2, was transferred into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

“Many drug candidates—especially those developed for neurodegenerative diseases—fail in clinical trials because current models don't accurately predict the drug's effects on the human brain,” said Dr. Yadong Huang, MD, PhD, Gladstone Institutes researcher and associate professor of neurology at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. “Human neurons—derived from reengineered skin cells—could help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials.”

Previously Unknown Stem Cell Is Real Culprit Behind Hardened Arteries

The guilty party is not the smooth muscle cells within blood vessel walls, which for decades were thought to combine with cholesterol and fat that can clog arteries. Instead, says new research, a previously unknown type of stem cell — a multipotent vascular stem cell — is to blame.

“For the first time, we have shown evidence that vascular diseases are actually a kind of stem cell disease,” said principal investigator Song Li, professor of bioengineering and a researcher at the University of California Berkeley Stem Cell Center. “This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target.”

The buildup of artery-blocking plaque has been thought to stem from the body’s immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets. Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.

Stem Cell Procedure Could End Need For Hip Replacements

The new procedure involves extracting stem cells from the bone marrow of patients in need of hip repair due to osteonecrosis, where poor blood supply causes significant bone damage.

These cells are mixed with cleaned, crushed bone from another patient who has had their own hip replaced and used to fill the hole made by surgeons after dead and damaged tissue has been removed from the joint.

“Although this work is still ongoing, several patients who have had the procedure have reacted very well and, if we get the results we are hoping for, these patients won’t need to have their hip joints replaced – they should be fixed completely,” said Doug Dunlop, a consultant orthopaedic surgeon at Southampton General Hospital.

“By using stem cells to send out chemical signals to blood vessels," said Professor Richard Oreffo, a specialist in musculoskeletal science at the University of Southampton, "we hope the body will continue to create new vessels in the hip which supply enough nutrients to maintain bone strength.”

Adapted from the University of Southhampton announcement.

New Technique Converts Stem Cells Into Brain Cells More Simply, More Quickly, and More Safely Than Previous Research Suggested Possible

By adding two molecules, researchers have discovered a surprisingly simple way of starting the stem cells' journey to become finished brain cells. The process mimics the brain's natural development by releasing signals that are part of the normal development process. Experiments in animal models have shown that the cells quickly adapt in the brain and behave like normal brain cells.

"We have used the new protocol to make dopamine neurons, the type of neuron that is affected by Parkinson's disease," said  Malin Parmar, associate professor of neurobiology at Lund University. "And for the first time, we are seriously talking about these cells as being good enough to move forward for transplantation in patients. The next step is to test the process on a larger scale and to carry out more pre-clinical safety tests."

Video: Drug Discovered That Destroys Human Cancer Stem Cells But Not Healthy Ones

The drug thioridazine apparently kills cancer stem cells in humans while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells by changing them into cells that are non-cancerous," said Mick Bhatia, scientific director of McMaster University's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells. The research team has identified another dozen drugs that have good potential for the same response.

 

Single Stem Cell Mutation Triggers Fibroid Tumors

Researchers have identified the molecular trigger of the uterin fibroid tumor, a single stem cell that develops a mutation, starts to grow uncontrollably and activates other cells to join its expansion.

The stem cell initiating the tumor carries a mutation called MED12. Once the mutation kicks off the abnormal expansion, the tumors grow in response to steroid hormones, particularly progesterone.

"No one knew how these came about before," said Serdar Bulun, M.D., chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital. "These stem cells

Osiris Therapeutics Prochymal, A Mesenchymal Stem Cell Product Derived From Bone Marrow, Approved For Marketing In Canada In Graft vs. Host Disease (GvHD)

Prochymal has been authorized for therapy in children with GvHD under Health Canada's Notice of Compliance with conditions (NOC/c) pathway, which provides access to therapeutic products that address unmet medical conditions and which have demonstrated a favorable risk/benefit profile in clinical trials. Under the NOC/c pathway, the sponsor must agree to carry out confirmatory clinical testing.

Both Osiris (OSIR) with Prochymal and Athersys Inc. (ATHX) with Multistem are in clinical trials with allogeneic GvHD stem cell therapies in the United States. Osiris concentrated on children after some issues arrose in its phase II clinical trial and has been aided in data presentation to Canadian authorities by Joanne Kurtzberg of Duke University. Athersys has not yet begun Phase II but has completed Phase I with good results.

Gene-Modified, Transplanted Blood Stem Cells Protect Brain Cancer Patients From Toxic Side Effects of Chemotherapy

Initial  results of the ongoing, small clinical trial of three patients with  glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

“We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells,” said Hans-Peter Kiem, M.D., a member of the Clinical Research Division at the Fred Hutchinson Cancer Center.

A major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

Communication Between Stem Cell Derived Motor Neurons, Muscle Cells Measured

Researchers have developed a novel system to measure communication between stem cell–derived motor neurons and muscle cells in a Petri dish.

In a proof of principle, they have shown that functional motor circuits can be created outside the body using stem cell–derived neurons and motor cells, and that the level of communication, or synaptic activity, between them can be accurately measured by stimulating the motor neurons with an electrode and then tracking the transfer of electrical activity into the muscle cells to which the neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells. This allows calcium and other ions to enter the cells, causing them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons.

The estimation could shed light on a variety of neurodegenerative diseases, such as spinal muscular atrophy and amyotrophic lateral sclerosis (Lou Gehrig's disease), in which communication between motor neurons and muscle cells is thought to unravel, said, Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Human Pluripotent Stem Cells Change During Expansion And Differentiation In Ways Not Easily Detected

Last year this research team reported recurrent changes in the genomes of human pluripotent stem cells as they are expanded in culture.

Now they have shown that these cells can also change their epigenomes, the patterns of DNA modifications that regulate the activity of specific genes—sometimes radically. These changes may influence the cells' abilities to serve as models of human disease and development.

"Our results show that human pluripotent stem cells change during expansion and differentiation in ways that are not easily detected, but that have important implications in using these cells for basic and clinical research," said Louise Laurent, assistant professor in the University of California San Diego School of Medicine.

Many avenues of stem cell research focus on determining how genes are turned on and off during the course of normal development or at the onset of a disease. It is widely accepted that gene activation and silencing play important roles in transforming all-purpose stem cells into the specific adult cell types that make up the specialized tissues of organs such as the heart and brain.

Here, Louise Laurent and Professor Jeanne Loring of Scripps Research focused on understanding gene silencing via DNA methylation, a process whereby bits of DNA are chemically marked with tags that prevent the genes from being expressed, effectively switching them off. Errors in gene silencing via DNA methylation are known contributors to serious developmental defects and cancer.

Specifically, they assessed the state of both DNA methylation and gene expression in the most comprehensive set of human stem cell samples to date, comprised of more than 200 human pluripotent stem cell samples from more than 100 cell lines, along with 80 adult cell samples representing 17 distinct tissue types.

Video: Stem Cell Therapeutic Solutions For Non-Healing Bone Fractures

Perhaps the area with the most promise for economic stem cell therapies in the near term is the healing of difficult fractures, a market where existing procedures total around $100 billion per year in the U.S. alone. Severe bone fractures can lead to such massive bone loss that realigning and fixing the bone with implants is not enough to heal the bone. In these cases, the trauma victim is left with chronic pain and non-functioning limbs.

In this video, Dr. Mark Lee, an orthopedic surgeon at the UC Davis School of Medicine, discusses new stem cell based methods to overcome these current challenges in treating non-healing bone. Techniques discussed are based on the use of mesenchymal stem cells. This took place on March 21, 2012.

 

New Method Found To Improve Stem Cell Delivery

It turns out that delivery of transplanted stem cells to a specific site in rodents is improved by increasing the presence of chemicals that attract the introduced cells.

Non-destructive pulsed and focused ultrasound interacts with tissue to elevate levels of naturally produced chemicals (such as cytokines, chemokines, and growth factors) on target tissues. Transplanted stem cells have receptors for these chemicals, so an increased presence attracts more of them to the desired site.

“It's like your circulatory system is a series of highways. What makes you want to get off at New York City? We're putting an attraction in the middle of nowhere so the transplant cells will want to go there, to the target site,” said Joseph A. Frank, M.D., chief of the NIH Clinical Center Radiology and Imaging Sciences Laboratory of Diagnostic Radiology Research.

Researchers Repair Damaged Hearts By Bypassing Induced Pluripotent Stem Cell Stage, Transforming Scar Tissue Directly Into Beating Heart Muscle

These researchers previously transformed scar-forming cardiac cells into beating heart muscle-like cells in petri dishes. Now they have accomplished this transformation in living animals, and with even greater success.

In laboratory experiments with mice that had experienced a heart attack, the team delivered three genes that normally guide embryonic heart development —together known as GMT — directly into the damaged region. Within a month, non-beating cells that normally form scar tissue transformed into beating heart-muscle cells. Within three months, the hearts were beating even stronger and pumping more blood.

“The damage from a heart attack is typically permanent because heart-muscle cells—deprived of oxygen during the attack—die and scar tissue forms,” said Dr. Deepak Srivastava MD, who directs cardiovascular and stem

Researchers Show Induced Pluripotent Stem Cells Can Be Ideal Model For Disease Research, Drug Testing

In a finding that adds to a growing body of evidence indicating that iPS cells can faithfully reflect the disease status of the patients from whom they are derived, researchers used induced pluripotent stem, or iPS, cell technology to create heart-muscle-like cells from the skin of patients with dilated cardiomyopathy, which is one of the leading causes of heart failure and heart transplantation in the United States.

Using newly created diseased and normal induced pluripotent stem cells, the researchers were able to directly observe for the first time the effect of a common beta blocker drug, as well as validate the potential usefulness of a gene therapy approach currently in clinical trials.

“Primary human cardiac cells are difficult to obtain and don’t live long under laboratory conditions,” said Joseph Wu, MD, PhD, associate professor of cardiovascular medicine at Stanford University. Instead, researchers have relied on studies of cells from rodent hearts, which beat much more quickly, to understand more about human heart disease.

Determining A Stem Cell's Fate

Researchers have traced the stepwise developmental process that ensures certain stem cells will become T cells—cells of the immune system that help destroy invading pathogens.

What happens to a stem cell at the molecular level that causes it to become one type of cell rather than another, the  point at which it is committed to that cell fate, and how it becomes committed, have unttil now been questions the answers to which have been largely unknown. As the specific answers to these questions evolve across a spectrum of stem cells and medical indications, much more directed clinical trials might be designed.

 "This is the first time a natural developmental process has been dissected in such detail, going from step to step to step, looking at activities of all the genes in the genome," said Ellen Rothenberg, Albert Billings Ruddock Professor of Biology at Caltech. "It means that in genetic terms, there is virtually nothing left hidden in this system."

Engineered Stem Cells Seek Out And Kill HIV In Living Organisms

In previous research, CD8 cytotoxic T lymphocytes — the "killer" T cells that help fight infection — were taken from an HIV-infected individual. The molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells was identified. However, these T cells, while able to destroy HIV-infected cells, do not exist in great enough quantities to clear the virus from the body.

To address this problem researchers cloned the receptor and used it to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.

In new research, the team engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.

Offspring Of Bone Marrow Derived Stem Cells Are Recruited To Repopulate Vascular Lining Of The Liver After Injury

After the partial surgical removal of rat livers, cells from the bone marrow are recruited to the liver and repopulate the vascular lining of the organ.

The recruited bone-marrow cells are called progenitor cells and are the offspring of stem cells. Once lodged in the liver, the progenitor cells become liver sinusoidal endothelial cells, the specialized cells that line the liver’s vascular system and perform a variety of functions. These progenitor cells also are a major source of hepatocyte growth factor, which stimulates liver-cell proliferation when a portion of a rat’s liver is removed.

Arsenic Spurs Tumor Growth By Turning Stem Cells Cancerous

That normal cells become cancerous when they are treated with inorganic arsenic has been previously determined by this same group of researchers. Their new research shows that when these cancer cells are placed close to -- but not in contact with -- normal stem cells, the normal stem cells very rapidly acquire the characteristics of cancer stem cells, demonstrating that malignant cells are able to send molecular signals through a semi-permeable membrane, where cells can't normally pass, and turn the normal stem cells into cancer stem cells.

"This paper shows a different and unique way that cancers can expand by recruiting nearby normal stem cells and creating an overabundance of cancer stem cells," said Michael Waalkes, Ph.D., Group Leader at the National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, part of NIH.

Phase II Study Finds Bone Marrow Stem Cells Improve Heart Function (Video)

In the context of a number of somewhat confusing recent research reports and trials involving bone marrow derived stem cells and heart therapy, a comparatively large phase II clinical trial has found that stem cells derived from heart failure patients own bone marrow and injected into their hearts improved the function of the left ventricle, the heart's pumping chamber.

Mayo Clinic cardiologist Dr. Robert Simari, chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), the network of five academic centers and associated satellite sites that conducted the study talks about the results in the following video:

 

Cardiac Stem Cells Outperform bone Marrow Stem Cells In Treating Heart Attacks

New research suggests that human fetal cardiac-derived c-kit+ stem cells (CSCs) can be 30 times more potent than bone marrow mesenchymal stem cells (MSCs) for treating a heart attack. 

As both of these cell types are currently in clinical trials, these results are significant because they are the first direct comparison of their therapeutic capability in vivo, the researchers say.

Researchers conducted the study using mice models with induced acute myocardial infarction. The mice then received human fetal CSCs or either an equivalent (low dose) or ~30-fold greater number (high dose) of MSCs.

New Method Developed To Create Mesenchymal Stem Cells From Either Embryonic Or Induced Pluripotent Stem Cells

Researchers have developed a new method to create mesenchymal stem cells (MSCs).

“We used a small molecule to induce embryonic stem cells over a 10 day period, which is much faster than other studies reported in the literature,” said Nicholas Fisk, professor of clinical research at the University of Queensland. “The technique also worked on their less contentious counterparts, induced pluripotent stem cells."

“To make the pluripotent mature stem cells useful in the clinic, they have to be told what type of cell they need to become (pre-differentiated), before being administered to an injured organ, or otherwise they could form tumours. Because only small numbers of MSCs exist in the bone marrow and harvesting bone marrow from a healthy donor is an invasive procedure, the ability to make our own MSCs in large number in the laboratory is an exciting step in the future widespread clinical use of MSCs."

“We were able to show these new forms of stem cells exhibited all the characteristics of bone marrow stem cells and we are currently examining their bone repair capability." 

Adapted from the University of Queensland announcement.

Providing Alternative To Induced Pluripotent Stem Cells, New Technique Promises To Enable Faster And More Efficient Production Of Functional Cells

New research has explored an alternative to iPS cells based on the use of transcriptional regulatory networks (TRNs), networks of transcription factors and the genes they regulate.

Previous research by this team had characterized the dynamic regulatory activities of these transcription factors during cellular differentiation from immature cells (monoblast) to developed (monocyte-like) cells using human acute monocytic leukemia cell lines (THP-1). The findings led them to hypothesize that functional characteristics of the cell-type are maintained by its specific TRN.

The new research has built on this hypothesis, establishing a series of new methods for identifying transcription factors (TFs) for the monocyte network, which play a key role in inducing cell-specific functions.

Four core TF genes of the monocyte TRN were introduced into human fibroblast cells. The expression of these genes activated monocytic functions including phagocytosis, inflammatory response and chemotaxis.

Genome-wide gene expression analysis of this reprogrammed cell showed a monocyte-like gene expression profile, demonstrating that reconstruction of a functional TRN can be achieved by introducing core TRN elements into unrelated cell types.

Adapted from the RIKEN Omics Science Center anouncement.

Eye Structures Produced From Human Blood-Derived Stem Cells

Researchers have made early retina structures containing proliferating neuroretinal progenitor cells using induced pluripotent stem (iPS) cells derived from human blood.

Additionally, the retina structures showed the capacity to form layers of cells (as the retina does in normal human development) possessing the machinery to allow them to communicate information. Together these findings suggest it's possible to assemble human retinal cells into more complex retinal tissues starting from a routine patient blood sample.

"We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain," said Dr. David Gamm, pediatric ophthalmologist and assistant professor of ophthalmology and visual sciences in the UW School of Medicine and Public Health.

Faster Way To Collect Stem Cells From Blood

It has been historically necessary to search through billions of other cells to collect rare cells such as tumor cells, stem cells or fetal cells. Reserchers at MIT and Massachusetts General Hospital have now demonstrated a new microfluidic device that can isolate target cells much faster than existing devices. 

Researchers have used a number of techniques to sort cells based on differences in size, density or electrical properties. However, since the physical characteristics of cells can vary significantly, these techniques risk separating cells incorrectly, leading to an erroneous diagnosis. A more specific way to isolate cells is to use antibodies that latch on to distinctive molecules displayed on the surfaces of the target cells.

Insulin And Diet Prevent Blood Stem Cell Differentiation In The Fruit Fly

Keeping blood stem cells, or progenitor cells, from differentiating into blood cells is important as blood stem cells are needed to create the blood supply for the adult fruit fly.

Now, a new study has found that the blood stem cells are receiving systemic signals from insulin and nutritional factors, in this case essential amino acids, that helped them to maintain their “stemness."

Researchers studied the flies in the larval stage of development. To see what would happen to the blood stem cells, larvae were placed into a jar with no food and left for 24 hours. Afterward, they checked for the presence of blood stem cells using specific chemical markers that made them visible under a confocal microscope.
 
“Once the flies were starved and not receiving the insulin and nutritional signaling, all the blood stem cells were gone,” said Ji Won Shim, a postdoctoral fellow in Banerjee’s lab. “All that were left were differentiated mature blood cells. This type of mechanism has not been identified in mammals or humans, and it will be intriguing to see if there are similar mechanisms at work there.”

Mechanism Determining Whether Embryonic Stem Cells Proliferate As Stem Cells Or Differentiate Into Adult Cells Proposed

New research has proposed a mechanism for the control of whether embryonic stem cells continue to proliferate and stay stem cells, or differentiate into adult cells like brain, liver or skin. 

In cancer treatment the goal is to inhibit cell proliferation. On the other hand, growing adult stem cells for transplantation therapy requires sustained proliferation until a sufficient number of cells have been produced to do the job. This new research provides an approach to controlling the two competing processes.

The new approach centers on a protein called Klf4 found in embryonic stem cells. Klf4 it seems keep cells dividing and proliferating rather than differentiating. The researchers found that two enzymes, ERK1 and ERK2, inactivate Klf which then allows the cells to begin differentiating into adult cells.

Specific MicroRNA In Resting Muscle Stem Cells Triggers Stem Cell Division

For the first time a small regulatory RNA, called a microRNA, has been implicated in the maintenance of the adult stem cell resting, or quiescent, state.

“Although on the surface the quiescent state seems to be relatively static, it’s quite actively maintained,” said Thomas Rando, MD, PhD, professor of neurology and neurological sciences, Stanford Medical School. “We’ve found that changing the levels of just one specific microRNA in resting muscle stem cells, however, causes them to spring into action.”

Unlike stem cells in the blood or skin, muscle stem cells spend most of their lives nestled in the surrounding tissue. 

“They don’t do much most of the time,” said Rando. “They remain in a quiescent state for most of a person’s life. When you injure your muscle, however, they begin dividing to repair the damage.” 

First-of-its-Kind Stem Cell Treatment Re-grows Healthy Heart Muscle in Heart Attack Patients

In what could be a major step forward for stem cell therapies, clinical trial patients who underwent a stem cell procedure demonstrated a significant reduction in the size of the scar left on the heart muscle by a heart attack. Patients also experienced a sizable increase in healthy heart muscle following the experimental stem cell treatments.

One year after receiving the stem cell treatment, scar size was reduced from 24 percent to 12 percent of the heart in patients treated with their own heart-derived cells (an average drop of about 50 percent). Patients in the control group, who did not receive stem cells, did not experience a reduction in their heart attack scars. 

"While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute. 

Researchers Discover How Infection Triggers Blood Stem Cell Growth

New findings show blood stem and progenitor cells can directly react to inflammatory stress by proliferating and differentiating into the required mature blood cells.

The discovery opens up a field of study into stem cells and how the blood system is “fine-tuned” in response to stressors. This new understanding of exactly how microbes signal to the stem cells has important implications for the treatment of infections and many diseases that have an inflammatory component, including cancer.

New Method Of Directing Stem Cells To Increase Bone Formation And Strength Developed

Directing stem cells to travel and adhere to the surface of bone for bone formation has been among the elusive goals in regenerative medicine. 

This new method enhances bone growth by using a unique hybrid molecule, LLP2A-alendronate. When injected into the bloodstream LLP2A-alendronate directs the body's stem cells to travel to the surface of bones. Once there the stem cells differentiate into bone-forming cells and synthesize proteins to enhance bone growth.

"There are many stem cells, even in elderly people, but they do not readily migrate to bone," said Wei Yao M.D., Assistant Professor, Center for Aging, UC Davis. "Finding a molecule that attaches to stem cells and guides them to the targets we need is a real breakthrough."

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."

Video: Irving Weisman On The Importance Of The Distinction Between Embryonic And Adult Stem Cells

The ethical argument concerning the use of embryonic stem cells continues to rage and may well be an issue in the upcoming 2012 election. The use of embryonic stem cells in research is continually questioned in some quarters on the premise that the growing success of adult stem cell research makes embryonic stem cell research unnecessary. In this four minute video Dr. Weissman explains what it's like to work with one type of cell versus the other and why the research distinction is important.

Irving Weissman is one of the older generation of stem cell pioneers.  He is a professor of pathology and developmental biology and the director of Stanford University School of Medicine's Institute of Stem Cell Biology and Regenerative Medicine.

 

In 1988, Dr. Weissman became the first to isolate in pure form any stem cell in any species when he isolated the hematopoietic or blood-forming stem cell in mice. He subsequently isolated the human hematopoietic stem cell, the human neuronal stem cell, and the human leukemia stem cell. 
Dr. Weissman's research encompasses the phylogeny and developmental biology of the cells that make up the blood-forming and immune systems.

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.

Factor That Translates Mechanical Work In Muscles Into Chemical Growth Signal To Muscle Stem Cells Found

We take it for granted, but the fact that our muscles grow when we work them makes them rather unique. Turns out a factor produced in working muscle fibers apparently tells surrounding muscle stem cells that it's time to multiply. In other words, this serum response factor (Srf) translates the mechanical signal of work into a chemical one.

"This signal from the muscle fiber controls stem cell behavior and participation in muscle growth," says Athanassia Sotiropoulos of Inserm in France. "It is unexpected and quite interesting."

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.

Flexible Neural Stem Cells Found In A Single Layer At The Back Of The Human Eye

That cell layer, known as the retinal pigment epithelium (RPE), underlies and supports photoreceptors in the light-sensitive retina. Without it, photoreceptors and vision are lost. The new study shows that the RPE also harbors self-renewing stem cells that can wake up to produce actively growing cultures when placed under the right conditions. They can also be coaxed into forming other cell types.

"You can get these cells from a 99-year-old," said Dr. Sally Temple, co-founder and scientific director of the Neural Stem Cell Institute in Rensselaer, New York. "These cells are laid down in the embryo and can remain dormant for 100 years. Yet you can pull them out and put them in culture and they begin dividing. It is kind of mind boggling."

Intervention With Young Stem Cells Makes Aging Mice Live Longer And Healthier

Mice bred to age too quickly seemed to have sipped from the fountain of youth after scientists at the University of Pittsburgh School of Medicine injected them with stem cell-like progenitor cells derived from the muscle of young, healthy animals.

Instead of becoming infirm and dying early as untreated mice did, animals that got the stem/progenitor cells improved their health and lived two to three times longer than expected. Previous research has revealed stem cell dysfunction, such as poor replication and differentiation, in a variety of tissues in old age, but it's not been clear whether that loss of function contributed to the aging process or was a result of it (see previous post).

Tissue Degeneration Found In Aging Is Partially Caused By Mitochondrial Dysfunction In Stem Cells

Research models have preciously found that an accumulation of mitochondrial genome defects leads to symptoms of premature aging: thin skin, graying of hair, baldness, osteoporosis and anemia.

In a breakthrough revealing the unexpected importance of energy metabolism in regulating stem cell function and tissue maintenance, new research on the mechanisms of age-associated degeneration indicates that tissue degeneration can be caused by mitochondrial dysfunction in tissue stem cells. Stem cell function may be modified with the result that progeny cells in blood and the nervous system are dysfunctional.

Stem Cell-Like Blood Progenitor Cells Receive Signals From Cells In Nearby Niche

These signals keep the progenitors in the same stem cell-like state so, when needed, they can begin differentiating into blood cells.

Now stem cell scientists have found that the blood progenitor cells receive critical signals back from the daughter blood cells they create, telling the progenitor cells when enough blood cells have been made and it's time to stop differentiating.

"The cells in the niche provide a safe environment to support blood progenitor cells," said Dr. Julian A. Martinez-Agosto, assistant professor of human genetics and pediatrics and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "When the blood progenitor cells receive signals from the niche cells it creates an environment for those cells to maintain their potential and not differentiate."

Molecules That Stimulate Stem Cells to Develop Into Beating Heart Muscle Cells Identified

To search for new molecules involved in heart development, the researchers developed a robust small molecule screen using a zebrafish system. The zebrafish is an excellent model organism to study heart growth and development because there are established genetic approaches that permit visualization of fluorescent beating hearts within the transparent embryos of zebrafish.

"Despite advances in modern medicine, management of myocardial infarction and heart failure remains a major challenge," Dr. Tao P. Zhong of Fudan University in Shanghai, China. "There is intense interest in developing agents that can influence stem cells to differentiate into cardiac cells as well as enhance the inherent regenerative capacities of the heart. Developing therapies that can stimulate heart muscle regeneration in areas of infarction would have enormous medical impact."