Stem Cell Research

Human Embryonic Stem Cells -- Transformed Into Nerve Cells -- Help Mice Regain Ability To Learn and Remember

Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine. "These two neuron types are involved in many kinds of human behavior, emotions, learning, memory, addiction and many other psychiatric issues," said Su-Chun Zhang, professor of neuroscience and neurology at the University of Wisconsin.

The transplanted cells were placed in the hippocampus (an interesting aside: see the release on Neuralstem Inc.'s Phase 1b trial regarding its neurogenic small molecule drug platform for hippocampal regeneration in MDD patients). After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialize and connect to the appropriate cells in the hippocampus.

After the transplant, the mice scored significantly better on common tests of learning and memory in mice.

Read the entire University of Wisconsin announcement here

Proof Of Principal Induced Neural Progenitor Stem Cell Solution To Parkinson's Disease

For the first time, researchers have transplanted neural cells derived from a monkey's skin into its brain and watched the cells develop into several types of mature brain cells.

In the research, iPS cells were converted into neural progenitor cells. The intermediate-stage cells have the ability to further specialize into  neurons that carry nerve signals, and glial cells that perform support and nutritional functions. This final stage of maturation occurred inside the three rhesus monkeys used in the experiment.

The rhesus monkeys used in the study at the Wisconsin National Primate Research Center had a lesion in a brain region that causes the movement disorder Parkinson's disease, which afflicts up to 1 million Americans. Parkinson's is caused by the death of a small number of neurons that make dopamine, a signaling chemical used in the brain.

Adapted from the University of Wisconsin announcement. Read further here.

Stem Cell 'Holy Grail' Closer: Encouraging Stem Cells to Turn Into The Cells Required To Treat a Specific Disease

Researchers have developed a web-like scaffold, coated with long-sugar molecules, that enhances stem-cell cultures to do just this. The scaffold is formed by a process known as ‘electrospinning’, creating a mesh of fibres that mimic structures that occur naturally within the body.

“These meshes have been modified with long, linear sugar molecules, which we have previously shown play a fundamental role in regulating the behaviour of stem cells," said Dr. Catherine Merry, from the University of Manchester’s Stem Cell Glycobiology group. "By combining the sugar molecules with the fibre web, we hoped to use both biochemical and structural signals to guide the behaviour of stem cells, in a similar way to that used naturally by the body. This is the Holy Grail of research into developing new therapeutics using stem cell technology.”

Read further from the University of Manchester announcement found here.

Bacteria Hide In Schwann Cells, Convert Them To Become Like Stem Cells

Researchers have found that bacteria are able to change the make-up of supporting Schwann cells within the nerve system so that they take on the properties of stem cells.  Scientists made the discovery studying bacteria that cause leprosy, which is an infectious neurodegenerative disease.

The study, carried out in mice, found that in the early stages of infection, the bacteria were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.
Like typical stem cells, these cells have the potential to become other cell types, for instance muscle cells. This enabled the bacteria to spread to tissues in the body.

Adapted from the University of Edinburgh announcement. Read further here.

Embryonic Stem Cells Demonstrated To Heal Damaged Artery

Cells derived from embryonic stem cells can repair experimentally damaged baboon arteries according to new research.

Cells lining the inside surface were removed from a segment of artery. Cells that had been derived from embryonic stem cells were then placed inside the artery.  Both ends of the arterial segment were then connected to plastic tubing inside a bioreactor which is designed to grow cells and tissues. Researchers then pumped fluid through the artery under pressure as if blood were flowing through it. The outside of the artery was bathed in another fluid to sustain the cells located there. 

Three days later, the complex structure of the inner surface was beginning to regenerate and by 14 days the inside of the artery had been perfectly restored to its complex natural state.

Adapted from the Texas Biomedical Research Institute announcement. Read further here.

Induced Pluripotent Stem Cell Stage Bypassed to Program Heart Attack Damaged Scar Tissue into Healthy Heart Muscle Using Genes

Researchers transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material.

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)

The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."

Adapted from the Weill Cornell Medical College announcement. Read further here.

Can The Human Body 'Coach' The Development Of Transplanted Stem Cells?

Exactly how to coax pluripotent stem cells to accomplish a therapeutic end while eliminating the possibility they may form dangerous tumors can vary widely among laboratories. Now researchers have used an experiment in mice to hit upon a way to possibly skip this fiddly step by instead relying mostly on signals within the patient's body to keep the stem cells in line.

“Once we identify the key proteins and signals coaching the tissue within the body, we can try to mimic them when we use the stem cells,” said Michael Longaker MD, professor at the Stanford School of Medicine. “Just as the shape of water is determined by its container, cells respond to external cues. For example, in the future, if you want to replace a failing liver, you could put the cells in a scaffold or microenvironment that strongly promotes liver cell differentiation and place the cell-seeded scaffold into the liver to let them differentiate in the optimal macroenvironment.”

Adapted and condensed from the Stanford School of Medicine announcement. Read further.

Cartiledge Produced From Induced Pluripotent Stem Cells

"This was a multi-step approach, with the initial differentiation, then sorting, and then proceeding to make the tissue," said  Brian O. Diekman, PhD, post-doctoral associate in orthopaedic surgery at Duke University. "What this shows is that Induced Pluripotent Stem Cells can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatments."

Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis. Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.

 Read further in the Duke University announcement.

Company Founded by Jamie Thomson Awarded $7M NIH Contract To Produce Induced Pluripotent Stem Cell Lines and Terminally Differentiated Tissue Cells

Jamie Thompson, who developed the first stem cell line in 1998 at the University of Wisconsin, published independent research on the creation of Induced Pluripotent Stem Cells (iPS cells) from human skin cells about two months later than Shinya Yamanaka who was just awarded the Nobel prize for his iPS results. Thomson, professor of Cell and Regenerative Biology at the University of Wisconsin School of Medicine, has long been an advocate for the use of iPS cells to study and test therapies in various chronic diseases due to the distinct advantage these cells offer. If iPS cells are produced from the adult cells of someone with Parkinson's disease, the cells will in all probability include the disease, allowing it, and therapies designed to fight it, to be studied in vitro. The same is true of other dibilitating diseases.

Now the NIH has awarded Cellular Dynamics International (CDUI), a private company founded by Jamie Thomson, a contract to provide human iPS cell lines and terminally differentiated tissue cells from normal or specified patient populations. The contract is worth up to $7.0 million for the three year life of the agreement.

 "This contract enables NIH researchers to easily access our human iPS cell-derived cells and accelerate the pace of their research," said Chris Parker, Chief Commercial Officer of CDI. "Scientists can now concentrate on their experiments and the data they generate instead of trying to manufacture a consistent and pure supply of human cells"

Read further in the Cellular Dynamics International announcement.

Similarities Found Between Cancer Cells And Induced Pluripotent Stem Cells

In new research, investigators compared iPSCs to a form of malignant cancer known as oncogenic foci that are also produced in laboratories; these cell types are used by medical researchers to create models of cancer, particularly sarcoma. Specifically, the scientists contrasted the different cells' transcriptomes, comprised of the RNA molecules or "transcripts."  Unlike DNA analysis, which reflects a cell's entire genetic code whether or not the genes are active, transcriptomes reflect only the genes that are actively expressed at a given time and therefore provide a picture of actual cellular activity.

From this transcriptome analysis, the investigators found that the iPSCs and malignant sarcoma cancer cells are unexpectedly similar in several respects. Genes that were not expressed in iPSCs were also not expressed in the cancer-generating cells, including many that have properties that guide a cell to normally differentiate in certain directions. Both cell types also exhibited evidence of similar metabolic activities, another indication that they are related cell types.

"This is the first study that describes the specific molecular pathways that iPSCs and cancer cells share from a direct comparison" said Paul Knoepfler, associate professor of cell biology and human anatomy at UC Davis. "It means that much more study is required before iPSCs can be used clinically. However, our study adds to a growing knowledge base that not only will help make stem cell therapies safer, but also provide us with new understandings about the cancer-causing process and more effective ways to fight the disease."

Condensed and adapted from the UC Davis announcement.

Regenerative Medicine at Wake Forest University with Dr. Anthony Atala

Dr. Anthony Atala has been a leader in the field of Regenerative Medicine, most particularly in the production of human organs. He discusses his work here in a second video following a brief introductory one.

Transplanted Neural Stem Cells Produce Myelin

Human neural stem cells developed by Stem Cells, Inc. were injected directly into the brains of four young children with an early-onset, fatal form of a condition known as Pelizaeus-Merzbacher disease (PMD). The neural stem cells successfully engrafted into the brains of patients and appear to have produced myelin.

Patients with early-onset PMD cannot walk or talk, often have trouble breathing and undergo progressive neurological deterioration leading to death as a result of an inherited genetic defect that prevents brain cells called oligodendrocytes from making myelin.

The investigators found evidence that the stem cells had successfully engrafted, receiving blood and nutrients from the surrounding tissue and integrating into the brain, a process that David H. Rowitch, MD, PhD, professor of pediatrics and neurological surgery at UCSF, chief of neonatology at UCSF Benioff Children’s Hospital and a Howard Hughes Medical Institute Investigator, likened to “a plant taking root.”

Condensed and adapted from the UCSF announcement.

Addition Of Certain Kinase Inhibitors Substantially Increases Production of Induced Pluripotent Stem Cells

Researchers have found that several kinase inhibitors produce many more Induced Pluripotent Stem Cells (iPSCs) than untreated cells, in some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

Induced Pluripoent Stem Cells hold promise as autologous and allogeneic therapeutic solutions. Perhaps even more importantly they can be produced from the adult cells of diseased individuals thus providing a perfect medium for the study of debilitating diseases. Issues regarding their use either in the laboratory or therapeutically involve both expansion methods and cost. This new research suggests solutions to both.

Stem Cell Digest postings on induced pluripotent stem cells include:

• Cedars-Sinai iPSC Core Production Facility
• iPSC Therapies Could Encounter Immune Rejection Problems
• Category: Induced Pluripotent Stem Cells
  

See the Sanford-Burnham Research Institute announcement.

Positive Interim Data From Spinal Cord Injury Trial Reported By StemCells, Inc.

StemCells Inc. reported that interim six-month data from the first patient cohort in a Phase I/II clinical trial of its HuCNS-SC product candidate -- purified human neural stem cells -- for chronic spinal cord injury demonstrates a favorable safety profile and shows gains in sensory function in two of the three patients compared to pre-transplant baselines. The third patient remains stable. The trial is being conducted in Zurich, Switzerland at the University Hospital Balgrist, University of Zurich. The trial is scheduled to end at 12 months.

In general stem cell therapeutic candidates have shown good saftey profiles in the phase one clinical trials both within and outside the United States. As phase II trials begin we will learn more about efficacy in various indications and much more will be known about the potential for actual therapies. Some Sector Companies are already hesitating at the door to Phase II awaiting investor or partner money to procede. In this context StemCells Inc. had net cash resources at June 30 of approximately $5 million. While The California Institute for Regenerative Medicine (CIRM) approved an award to StemCells Inc. for up to $20 million under CIRM's Disease Team Therapy Development Award program (RFA 10-05), the award is to fund preclinical development of StemCells' purified human neural stem cells product candidate as a potential treatment for cervical spinal cord injury.

Patients in the study's first cohort all suffered a complete injury to the thoracic (chest-level) spinal cord. In a complete injury, there is no neurological function below the level of injury. All three patients were transplanted four

Crucial Role Of Protein Found: Preserves 'Stemness' In Stem Cells, Primes Them To Become Specialized

Researchers have zeroed in on the factors that add temporary tags to DNA when it’s coiled around tiny spools called histones. In order to read their DNA, stem cells have to unwind it a bit from those spools, allowing the gene-reading mechanisms to get access to the genetic code and transcribe it. The temporary tags added by a protein called Mof act as tiny beacons, guiding the “reader” mechanism to the right place.

These results show that Mof plays a key role in the “epigenetics” of stem cells -- that is, helping stem cells read and use their DNA. One of the key questions in stem cell research is what keeps stem cells in a kind of eternal youth, and then allows them to start “growing up” to be a specific type of tissue.

“Simply put, Mof regulates the core transcription mechanism – without it you can’t be a stem cell,” said  Yali Dou, Ph.D, associate professor of pathology and biological chemistry at the University of Michigan. “There are many such proteins, called histone acetyltransferases, in cells – but only MOF is important in undifferentiated cells.”

Blood Vessels Made From Skin Cells Reprogrammed Through Induced Pluripotent Stem Cell Stage

Researchers in England have made the first artificial functioning blood vessel outside of the body by reprogramming stem cells from human skin. The researchers also saw the cells develop into a blood vessel inside the body for the first time.

Stem cell therapy to treat heart disease is already being carried out in the clinic using bone marrow cells, however, the long-term effectiveness at the moment is minimal and some types of stem cells have the potential to become a tumour after they are introduced into the body.

This new research demonstrates that a new type of partial stem cell developed from fibroblasts (skin cells) can be reprogrammed into vascular cells before going into the body, which have no risk turning into tumours.

New Neural Stem Cell Population Identified; May Be Stem Cell Responsible For Higher Levels Of Thought, Conciousness

The new research reveals how neurons in the uppermost layers of the cerebral cortex form during embryonic brain development. The stem cell discovery may provide a first step in developing better treatments for cognitive disorders, such as schizophrenia and autism, which result from disrupted connections among these brain cells.

“The cerebral cortex is the seat of higher brain function, where information gets integrated and where we form memories and consciousness,” said Ulrich Mueller, a professor and director of the Dorris Neuroscience Center at Scripps Research. “If we want to understand who we are, we need to understand this area where everything comes together and forms our impression of the world.”

Mueller’s team identified a neural stem cell in mice that specifically gives rise to the neurons that make up the upper layers of the cerebral cortex. Previously, it was thought that all cortical neurons—those making up both the lower and upper layers—came from the same type of stem cell, called a radial glial cell, or RGC. A

Induced Pluripotent Stem Cells Produced With Mutated Parkinson's Gene

Using adult stem cells, researchers have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage. Working as part of a National Institute of Neurological Disorders and Stroke consortium, the team created three lines of induced pluripotent stem (iPS) cells derived from the skin cells of adults with PD. Two of the cell lines had the mutated LRKK2 gene, a hallmark of the most common genetic cause of PD.

“Our study suggests that some failed drugs should actually work if they were used earlier, and especially if we could diagnose PD before tremors and other symptoms first appear,” said Ted M. Dawson, M.D., Ph.D., a professor of neurology at the Johns Hopkins University School of Medicine.

Environmental Factors Critically Influence Induced Pluripotent Stem Cell Development

Researchers have discovered that environmental factors critically influence the growth of Induced Pluripotent Stem Cells  (IPS cells) that are derived from adult skin cells. For the first time, researchers have shown that protein factors released by other cells affect the “reprogramming” of adult cells into stem cells.

“We’ve reinforced our hypothesis that the cell’s environment is vital to the reprogramming process,” said Gladstone Senior Investigator Shinya Yamanaka MD, PhD, a professor at UCSF. “We can now expand our understanding of cell development — and use iPS cells to model conditions such as Alzheimer’s and heart disease.”

Amniotic Fluid Yields Alternatives To Embryonic Stem Cells

Research findings raise the possibility stem cells derived from donated amniotic fluid could be stored and used for therapies and in research, providing a viable alternative to the limited embryonic stem cells currently available.

Researchers used stem cells from amniotic fluid donated by mothers undergoing amniocentesis for other purposes during the first trimester of pregnancy. The cells were grown on a gelatinous protein mixture in the lab and reprogrammed into a more primitive state by adding a drug called valproic acid to the culture medium.

Extensive tests found that these reprogrammed cells have characteristics very similar to embryonic stem cells.

“Amniotic fluid stem cells are intermediate between embryonic stem cells and adult stem cells. They have some potential to develop into different cell types but they are not pluripotent," said Dr Pascale Guillot, Department of Surgery and Cancer at Imperial College London. "We’ve shown that they can revert to being pluripotent just by adding a chemical reagent that modifies the configuration of the DNA so that genes that are expressed in the embryo get switched back on."

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.”

Blood-Brain Barrier Building Blocks Generated From Human Stem Cells

The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it.

However, the barrier can be disrupted by disease, stroke and multiple sclerosis, for example, and also is a big challenge for medicine, as it can be difficult or impossible to get therapeutic molecules through the barrier to treat neurological disorders.

Now researchers have transformed stem cells into endothelial cells with blood-brain barrier qualities in a laboratory dish in an attempt to get the blood-brain barrier to share its secrets.

“The nice thing about deriving endothelial cells from induced pluripotent stem cells is that you can make disease-specific models of brain tissue that incorporate the blood-brain barrier,” explains Sean Palecek, a UW-Madison professor of chemical and biological engineering. “The cells you create will carry the genetic information of the condition you want to study.”

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.

Jamie Thomson's Cellular Dynamics International To Partner With Life Technologies In Global Commercialization of Novel Stem Cell Technologies

Life Technologies Corporation (LIFE), a 7 billion dollar global life sciences company, today announced a partnership with Cellular Dynamics International (CDI), , the world’s largest producer of human cells derived from induced pluripotent stem (iPS) cells, to commercialize a set of three new products optimized to consistently develop and grow human iPS cells for both research and bioproduction.

Cellular Dynamics International, Inc. (CDI), founded by induced pluripotent stem cell pioneer, Jamie Thomson, professor, University of Wisconsin,  is a currently private developer of next-generation stem cell technologies for drug development, cell therapy, tissue engineering and organ regeneration. Jamie Thomson is a strong advocate for the use of Induced Pluripotent Stem cells in drug testing and development.

CDI uses a unique manufacturing technology to produce differentiated tissue cells from any individual’s stem cell line in industrial quality, quantity and purity. The company is attempting to accelerate the adoption of pluripotent stem cell technology, adapting its methods to fit into standard clinical practice by the creation of individual stem cell lines from a standard blood draw.

The partnership marries CDI’s human iPS cell development with Life Technologies’ expertise in stem cell research tool manufacturing as well as its global distribution network to make these technologies

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.”

New Stem Cell Technique Promises Inexpensive, Efficient Method To Produce Abundance Of Key Heart Cells From Stem Cells

There seems to be a trend developing around faster and cheaper means of producing human cells with therapeutic value from stem cells (post). In the newest research, cardiomyocytes, the workhorse cells that make up the beating heart, can now be made cheaply and abundantly in the laboratory.

The new technique transforms human stem cells — both embryonic and induced pluripotent stem cells — into these critical heart muscle cells by simple manipulation of one key developmental pathway. It promises a uniform, inexpensive and far more efficient alternative to the complex bath of serum or growth factors now used to nudge blank slate stem cells to become specialized heart cells.

"We have been able to reliably generate greater than 80 percent cardiomyocytes in the final population while other methods produce about 30 percent cardiomyocytes with high batch-to-batch variability," said Sean Palecek, University of Wisconsin-Madison professor of chemical and biological engineering.

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."

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.

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 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."

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.

Stem Cells Hint At Treatment For Huntington's Disease

Huntington's disease is a debilitating congenital neurological disorder that progressively robs patients of muscle coordination and cognitive ability.

Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist, is expert at making different types of brain cells from human embryonic or induced pluripotent stem cells. In the new research, his team focused on what are known as GABA neurons, cells whose degradation is responsible for disruption of a key neural circuit and loss of motor function in Huntington's patients. GABA neurons produce a key neurotransmitter, a chemical that helps underpin the communication network in the brain that coordinates movement.

Zhang has learned how to make large amounts of GABA neurons from human embryonic stem cells, which he sought to test in a mouse model of Huntington's disease. The goal of the study was simply to see if the cells would safely integrate into the mouse brain. To their astonishment the cells not only integrated but also projected to the right target and effectively reestablished the broken communication network, restoring motor function.

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.

First Step in Induced Pluripotent Stem Cell Replacement Therapy in Parkinson’s Disease Undertaken

Japanese researchers have found induced pluripotent stem cells (iPSC) to be a promising avenue for cell replacement therapy in neurologic diseases. Mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that demonstrate improved symptoms in rat Parkinson’s disease models. 

 “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.” 

Sigma Life Science Gains Rights to Induced Pluripotent Stem Cell Technology Developed By Kyoto University

Induced Pluripotent Stem Cell (iPSC) technology can create pluripotent stem cells from the normal adult cells of a patient. Pluripotent stem cells are capable of differentiating into many specialized primary cell types needed for research, such as cardiomyocytes, hepatocytes, neurons, and muscle cells.

With access to differentiated cells from patients with the condition of interest, or healthy human cells engineered to contain disease-specific genetics, researchers may obtain greater predictive accuracy than is possible with the in vitro models used currently in pharmaceutical research and preclinical studies.

Sigma says the licensed technology will enable it to develop new tools for drug discovery and preclinical research, including iPSCs, iPSC-derived primary cells, assays, custom cell lines, and ADME/Tox services.

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