Stem Cell Research

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.

Signaling Molecule May Help Stem Cells Focus To Limit Or Prevent Bone Loss in Aging

New research suggests a signaling molecule that helps stem cells survive in the naturally low-oxygen environment inside bone marrow may hold clues to helping the cells survive when the going gets worse with age and disease.

They’ve found that inside the usual, oxygen-poor niche of mesenchymal stem cells, stromal cell-derived  factor-1, or SDF-1, turns on a survival pathway called autophagy that helps the cells stay in place and focused on making bone.

Unfortunately with age or disease, SDF-1 appears to change its tune, instead reducing stem cells’ ability to survive and stay in the bone marrow, said Samuel Herberg, Georgia Regents University graduate student.  Additionally cells that do stay put may be less likely to make bone and more likely to turn into fat cells in the marrow.

The researchers believe it’s the changes in the normal environment that come with age or illness, including diminished nutrition, that prompt SDF-1’s shifting role.

“You put new cells in there and, all of the sudden, you put them in a neighborhood where they are being attacked,” said Dr. William D. Hill, stem cell researcher at the Medical College of Georgia at Georgia Regents University. “If we can somehow precondition the transplanted cells or modify the environment they are going into so they have higher levels of autophagy, they will survive that stress.”

Adapted from the Georgia Regents University announcement. Read further here.

Discovery in Bone Marrow May Improve Chemotherapy, Stem Cell Transplants

The new findings, in mice, suggest that it may be possible to therapeutically target support cells in a particular niche. On the one hand, a drug that nourishes support cells could encourage blood stem cells to establish themselves in the bone marrow, enabling patients who have had stem cell transplants to more quickly rebuild their immune systems.

“Our results offer hope for targeting these niches to treat specific cancers or to improve the success of stem cell transplants,” says senior author Daniel Link, MD, Professor of Medicine at Washington University in St. Louis. “Already, we and others are leading clinical trials to evaluate whether it is possible to disrupt these niches in patients with leukemia or multiple myeloma.”

Working in the mice, the researchers selectively deleted a critical gene, CXCL12, which is known to be important for keeping blood stem cells healthy. Rather than knock out the gene in all of the support cells in a niche, the researchers deleted the gene in specific types of support cells. This led to the discovery that each niche holds only certain blood stem cells that are nourished by a unique set of support cells.

Adapted from the University of Washington in St. Louis announcement. Read further here.

Related post.

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.

New Research Documents Different Niches For Blood-Forming Stem Cells

New research has identified niches for stem cells and early lymphoid progenitors by determining which cells are the sources of a growth factor (CXCL12) necessary for the proliferation of those two populations of blood-forming cells. By taking the same approach for other growth factors in the bone marrow, researchers should be able to map the niches for every kind of blood-forming progenitor cell in the bone marrow.

“In understanding the environments for blood-forming stem cells and those of different kinds of progenitor cells," said Dr. Sean Morrison, Director of the Institute and Professor of Pediatrics at UT Southwestern Medical Center, "we can work toward reproducing those environments in the lab and growing cells that can be transplanted to treat a host of medical conditions.”

Scientists already know how to manufacture large quantities of stem cells that give rise to the nervous system, skin, and other tissues. But they have been unable to make blood-forming stem cells in a laboratory, in part because of a lack of understanding about the niche in which blood-forming stem cells and other progenitor cells reside in the body.

Read further from the University of Texas Southwestern Medical School announcement here.

Stem Cell Research Helps to Identify Origins of Schizophrenia

New research suggests defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.

The genomic pathway, called the Integrative Nuclear FGFR 1 Signaling (INFS), is a central intersection point for multiple pathways of as many as 160 different genes believed to be involved in the disorder.

“We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” says lead author Michal Stachowiak, PhD, professor in the Department of Pathology and Anatomical Sciences in the University of Buffalo School of Medicine and Biomedical Sciences.

A key challenge with the disease is that patients with schizophrenia exhibit mutations in different genes, according to Dr. Stachowiak.

“How is it possible to have 100 patients with schizophrenia and each one has a different genetic mutation that causes the disorder?” asks Stachowiak. “It’s possible because INFS integrates diverse neurological signals that control the development of embryonic stem cell and neural progenitor cells, and links pathways involving schizophrenia-linked genes.

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

Stem Cell Discovery Identifies Potential Obesity Treatment

Researchers have discovered a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity.

"This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese," says Dr. Rudnicki, a senior scientist and director for the Regenerative Medicine Program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute.

This new research demonstrates that adult muscle stem cells not only have the ability to produce muscle fibres but also to become brown fat. Brown fat is an energy-burning tissue that is important to the body's ability to keep warm and regulate temperature.

Adapted from the Ottawa Hospital Research Institute announcement. Read further here.

Diabetes Distresses Bone Marrow Stem Cells By Damaging Their Microenvironment

New research has shown the presence of a disease affecting small blood vessels, known as microangiopathy, in the bone marrow of diabetic patients. While it is well known that microangiopathy is the cause of renal damage, blindness and heart attacks in patients with diabetes, this is the first time that a reduction of the smallest blood vessels has been shown in bone marrow, the tissue contained inside the bones and the main source of stem cells.

The researchers have shown a profound remodelling of the marrow, which shows shortage of stem cells and surrounding vessels mainly replaced by fat, especially in patients with a critical lack of blood supply to a tissue (ischaemia).  This means that, as peripheral vascular complications progress, more damage occurs in the marrow. In a vicious cycle, depletion of bone marrow stem cells worsens the consequences of peripheral ischaemia.

Professor Paolo Madeddu, Chair of Experimental Cardiovascular Medicine in the School of Clinical Sciences and Bristol Heart Institute at the University of Bristol, said: “Our study draws attention to the bone marrow as a primary target of diabetes-induced damage.  The research suggests that the severity of systemic vascular disease has an impact on bone marrow causing a precocious senescence of stem cells.  More severe bone marrow pathologies can cause, or contribute to, cardiovascular disease and lead to worse outcomes after a heart attack, through the shortage of vascular regenerative cells.  Clinical evidence indicates that achieving a good control of glucose levels is fundamental to prevent vascular complications, but is less effective in correcting microangiopathy.  We need to work hard to find new therapies for mending damaged microvessels.”

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

Stem Cell Therapy Shown to Recruit Body's Own Stem Cells That Mature Then Into Heart Cells

The same research team demonstrated that stem cell therapy reduces scarring and regenerates healthy tissue after a heart attack in a 2012 clinical trial. Now they have found that the stem cell technique boosts production of existing adult heart cells (cardiomyocytes) and spurs recruitment of existing stem cells that mature into heart cells.

“We’re finding that the effect of stem cell therapy is indirect. It stimulates proliferation of dormant surviving host heart tissue, and it attracts stem cells already in the heart. The resultant new heart muscle is functional and durable, but the transplanted stem cells themselves do not last long,” said Eduardo Marbán, MD, PhD, director of the Cedar-Sinai Heart Institute.

The investigational therapy turns on genes that bolster cell production from both sources – existing heart cells and existing stem cells – essentially boosting the heart’s normal means of cell replacement and its natural responses to injury. The injection of stem cells also improves heart structure and function.

Adapted from the Cedars-Sinai announcement. Read further here.

Stem Cell Approach Shows Promise For Duchenne Muscular Dystrophy

Researchers have shown that transplanting stem cells derived from normal mouse blood vessels into the hearts of mice that model the pathology associated with Duchenne muscular dystrophy (DMD) prevents the decrease in heart function associated with DMD.

In the new study, researchers injected stem cells known as aorta-derived mesoangioblasts (ADM) into the hearts of dystrophin-deficient mice that serve as a model for human DMD. The ADM stem cells have a working copy of the dystrophin gene.

This stem cell therapy prevented or delayed heart problems in mice that did not already show signs of the functional or structural defects typical of Duchenne muscular dystrophy.

Adapted from the University of Illinois announcement story. Read further 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.

Knee Cartilage Repair A Success Using New Biomaterial to Influence Autologous Stem Cells

Researchers are reporting increased healthy tissue growth after surgical repair of damaged cartilage where “hydrogel” scaffolding is placed in the wound to support and nourish the healing process.

The squishy hydrogel material was implanted in 15 patients during standard microfracture surgery, in which tiny holes are punched in a bone near the injured cartilage. The holes stimulate the patients’ own specialized stem cells to emerge from bone marrow and grow new cartilage atop the bone.

“Our pilot study indicates that the new implant works as well in patients as it does in the lab, so we hope it will become a routine part of care and improve healing,” says Jennifer Elisseeff, Ph.D., Professor of Ophthalmology and Biomedical Engineering and director of the Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC).

Adapted from the Johns Hopkins Medicine 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.

Transplanted Neural Stem Cells Treat ALS In Mouse Model

Eleven independent studies show that transplanting neural stem cells into the spinal cord of an ALS mouse model slows disease onset and progression, improves motor function, and significantly prolongs survival.

The transplanted neural stem cells did not benefit ALS mice by replacing deteriorating nerve cells. Instead, neural stem cells help by producing factors that preserve the health and function of the host’s remaining nerve cells. They also reduce inflammation and suppress the number of disease-causing cells in the host’s spinal cord.

Read further in the Sanford Burnham Medical Research Institute announcement.

Note: Neuralstem Inc. (CUR), one of our Sector Companies, is preparing for a phase II clinical trial involving transplanted neural stem cells for ALS.

New Stem Cell Delivery Technique May Repair Damaged Or Diseased Corneas

Researchers have developed a new method for producing membranes to help in the grafting of stem cells onto the eye, mimicking structural features of the eye itself. The technology has been designed to treat damage to the cornea, the transparent layer on the front of the eye, which is one of the major causes of blindness in the world.

Using a combination of techniques known as microstereolithography and electrospinning, the researchers are able to make a disc of biodegradable material which can be fixed over the cornea. The disc is loaded with stem cells which then multiply, allowing the body to heal the eye naturally.

“The disc has an outer ring containing pockets into which stem cells taken from the patient’s healthy eye can be placed,” said Dr Ílida Ortega Asencio, from the University of Sheffield’s Faculty of Engineering.

Read further in the University of Sheffield announcement.

Creation Of Implantable Cartilage Accomplished With Novel Hybrid Printer

 The printing of 3D tissue has taken a major step forward with the creation of a novel hybrid printer that simplifies the process of creating implantable cartilage.

The printer is a combination of two low-cost fabrication techniques: a traditional ink jet printer and an electrospinning machine. Combining these systems allowed the scientists to build a structure made from natural and synthetic materials. Synthetic materials ensure the strength of the construct and natural gel materials provide an environment that promotes cell growth.

In this study, the hybrid system produced cartilage constructs with increased mechanical stability compared to those created by an ink jet printer using gel material alone. The constructs were also shown to maintain their functional characteristics in the laboratory and a real-life system.

Read the full story from Wake Forest University in the IOP Institute of Physics journal

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.

New Tactic For Manipulating Human Blood Stem Cells Found: Non-Coding RNA called miRNA

Stem cell researchers have discovered a new “master control gene” for human blood stem cells and found that  manipulating its levels could potentially create a way to expand these cells for clinical use.

“For the first time in human blood stem cells, we have established that a new class of non-coding RNA called miRNA represents a new tactic for manipulating these cells, which opens the door to expanding them for therapeutic uses,” says Dr. John Dick, Professor in the Department of Molecular Genetics, University of Toronto. “We’ve shown that if you remove the miRNA you can expand the stem cells while keeping their identity intact. That’s the key to long-term stem cell expansion for use with patients.”

The researchers removed a master control gene  – microRNA 126 (miR-126) – that normally governs the expression of hundreds of other genes by keeping them silenced, which in turn keeps the stem cells in a non-dividing dormant state. The method was to introduce excess numbers of miR-126 binding sites into the stem cells by using a specially designed viral vector.

Condensed from the McEwen Center for Regenerative Medicine announcement.

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.

No Adverse Events Associated With First 10 Patients In World's First Intra-Arterial Clinical Trial For Ischemic Stroke

Preclinical research, including research at the UTHealth Medical School, has suggested that stem cells can promote the repair of the brain after an ischemic stroke caused by a blood clot in the brain.

The trial -- the only randomized, double-blind, placebo-controlled intra-arterial clinical trial in the world for ischemic stroke -- is studying the safety and efficacy of a regenerative therapy developed by Aldagen Inc., a wholly-owned subsidiary of Cytomedix, Inc. (CMXI), that uses a patient’s own bone marrow stem cells administered between 13 and 19 days post-stroke.

Unerstanding How Resident Stem Cells And Stem Cell Transplants Improve Brain Function

The brain’s key “breeder” cells secrete substances that boost the numbers and strength of critical brain-based immune cells believed to play a vital role in brain health.

“Transplanting neural stem cells into experimental animals’ brains shows signs of being able to speed recovery from stroke and possibly neurodegenerative disease as well,” said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences in the Stanford School of Medicine. “Why this technique works is far from clear, though, because actually neural stem cells don’t engraft well.”

While of critical importance to maintaining healthy brain function, true neural stem cells are rare. Far more common are their immediate progeny, which are called neural progenitor cells, or NPCs. These robust, rapidly dividing cells are poised to travel down a committed path of differentiation to yield new brain cells of several different types including neurons.

One category of brain cells, microglia, descends not from neural stem cells but from an immune lineage and retains several features of immune cells. “Microglia are the brain’s own resident immune cells,” Wyss-Coray said. Unlike most other mature brain cells, microglia can proliferate throughout adulthood, especially in response to brain injury. They can, moreover, migrate toward injury sites, secrete various “chemical signaling” substances, and gobble up bits of debris, microbial invaders or entire dead or dying neurons.

In a series of experiments, Wyss-Coray and his colleagues have shown that neural progenitor cells secrete substances that activate microglia...

Read more in the Stanford University School of Medicine 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.

Rare, Previously Unknown Sub-Group Of Activated Immune Cells Keep Stem Cells In Bone Marrow "Forever Young"

Researchers have found that a rare sub-population of bone-marrow macrophages -- literally the “big eaters” of the immune system -- has another role to play: Each of these rare macrophages can take a stem cell under its wing and prevent its differentiation.

These macrophages guard the stem cells by secreting substances called prostaglandins, which are absorbed by the stem cells. In a chain of biochemical events, these substances delay differentiation and preserve the youthful state of the stem cells.

In addition, the prostaglandins work on the neighboring mesenchymal cells, activating the secretion of a delaying substance in them and increasing the production of receptors for this substance on the stem cells, themselves. This activity, said Professor Tsvee Lapidot of the  Weismann Institute’s immunology Department, may help the non-dividing stem cells survive chemotherapy – a known phenomenon. Macrophages also live through the treatment, and they respond by increasing their prostaglandin output, thus heightening their vigilance in protecting the stem cells.

Read further in the Weizman Institute's 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.

Epigenetic Changes In Adult Stem Cells Generate Different Tissues In The Human Body

The genome of every cell in the human body is the same, regardless of function. Therefore the activity of the tissues and organs in complex diseases, cancer being a prime example, cannot be fully explained by the genome.

Part of the explanation is provided by epigenetics, defined as, "a set of chemical reactions that switch parts of the genome off and on at strategic times and locations."

In this study, researchers have isolated stem cells from body fat and transformed them into muscle and bone cells.

Read more in the IDIBELL announcement.

Biological Process Used By Salamanders to Regenerate Severed Limbs Found In Small South African Mammal

For years biologists have studied salamanders for their ability to regrow lost limbs. However, no such regenerative capacity has been seen in mammals with the exception of a few tails.

“The African spiny mouse appears to regenerate ear tissue in much the way that a salamander regrows a limb that has been lost to a predator,” said Ashley W. Seifert, a postdoctoral researcher in the University of Florida’s biology department. “Skin, hair follicles, cartilage — it all comes back.”

Seifert used a 4mm biopsy punch, about the size of a large BB, to puncture holes in the ears of the mice to see if the animal showed regenerative capabilities.

“The results were astonishing,” he said. “The various tissues in the ear grew back through formation of blastema-like structures — the same sort of biological process that a salamander uses to regenerate a severed limb.”

Condensed and adapted from the University of Florida announcement.

Seeking Alpha and Neuralstem's Continuing ALS and MDD Trials

This morning Seeking Alpha ran an article suggesting that Neuralstem Inc.'s (CUR) stock price might be flat for an extended period. This is interesting and unlikely for at least three reasons:

First, CUR has closed at prices varying from $0.45 to $1.42 since August 24. Two stock offerings have closed since mid August, one priced at $.040 and the follow up at $1.00.

Second, during the same period CUR has announced good results from both clinical and pre-clinical trials. The roller coaster ride in stock price has resulted from positive trial results versus the two dilutive events.

Third, in the two clinical trials CUR has underway, one for amyotrophic lateral sclerosis (ALS) and the other for major depresive disorder (MDD) -- this trial is particularly unique -- CUR will report results by the end of 2012 or in the first calendar quarter of 2013.

Read info on the ALS trial here, and the MDD trial here.

Researchers Seek To Instruct Human Stem Cells Using Molecules The Cells Already Use To communicate With One Another

For several years researchers have worked with two cellular communication molecules — sonic hedgehog and ephrin ligands — that factor into how a stem cell determines which blueprint to work from when it is differentiating into a specific cell type. As a result they can now explain the role that ephrin ligands play in creating the proper circumstances for adult neurogenesis, the process by which stem cells can become neurons.

"Basically, a stem cell can 'sense' what's in its environment, and then it makes a decision to determine whether it's going to become a muscle cell or a brain cell," said Randy Ashton, a University of Wisconsin-Madison assistant professor of biomedical engineering..

Using recombinant "mimic" forms of each molecule to instruct the stem cells and a biodegradable 3-D scaffold to hold a cluster of cultures together, Ashton has grown increasingly complex tissue structures, specializing in the central nervous system.

Read more in the Universiy of Wisconsin Madison 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.

Research Suggests Promise of Stem Cell Therapy for Bowel Disease

New research shows that a special population of stem cells found in cord blood has the innate ability to migrate to the intestine and contribute to the cell population there, suggesting the cells’ potential to treat inflammatory bowel disease (IBD).

Unrelated to the research in this study, Athersys (ATHX), with it's product candidate, Multistem, is in a Phase II trial in the United States for Inflammatory bowel disease in association with Pfizer.

“These cells are involved in the formation of blood vessels and may prove to be a tool for improving the vessel abnormalities found in IBD,” said lead author Graca Almeida-Porada, M.D., Ph.D., a professor at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine.

While there is currently no cure for IBD, there are drug therapies aimed at reducing inflammation and preventing the immune response. However, these therapies aren’t always effective. The long-term aim of the research is to develop an injectable cell therapy to induce tissue recovery.

The researchers studied a special population of cells, known as endothelial colony-forming cells, found in

Researches Find Suppressor Genes Vital to Regulating Stem Cell-Like Precursor Cells

Much research is being done on stem cell boundaries. How does an embryo know in advance what size the spleen, liver or ears should be. How do stem cells know when to stop? And in the adult body how do stem cells know when repair is necessary? Of how far to go in creating new cells?

"How does an organism know how many blood cells to make and when to make them in the context of injury and repair to tissue," said UCLA's Dr. Julian A. Martinez-Agosto, the senior author of the study. "In particular, we wondered how the blood progenitor cells sense that change and know when it's time to make more blood cells."

To answer this question, Martinez-Agosto, an 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, and colleagues examined a signaling pathway called TOR that the cells use to gauge nutrition levels and stress.

Nine Genes At Heart Of Epigenetic Changes In Induced Pluripotent Stem Cells

In 2006, scientists discovered how to revert mature cells, which had already differentiated into particular cell types, such as skin cells or hair cells, back into a pluripotent state. These "induced pluripotent stem cells" (iPSCs), which could be developed from the patient's own cells, would theoretically carry no risk of immune rejection.

However, scientists found that iPSCs had molecular differences from embryonic stem cells. Specifically, there were epigenetic changes, chemical modifications in DNA that might alter genetic activity. At certain points in the iPSC's genome, scientists could see the presence of different patterns of methyl groups when compared to the genomes of ESCs. It seemed these changes occurred randomly.

Unlike previous studies, which had primarily analyzed iPSCs derived from only one mature type of cells (mainly connective tissue cells called fibroblasts), Salk and UCSD researchers examined iPSCs derived

Researchers Provide New Insights into Muscle Stem Cells

Muscle stem cells colonize a niche located between the plasma membrane of the muscle cell and the surrounding basal lamina. These niches contain muscle stem cells from which both muscle cells and new stem cells are generated, even in newborn babies.

New research has shown that mouse muscle progenitor cells lacking components of the Notch signaling pathway cannot colonize their niche. Instead the muscle progenitor cells locate in tissue between the muscle fibers and cause a weakening of the muscles.

Researchers also found the Notch signaling pathway to have a second function in muscle development, that of preventing the differentiation of stem cells into muscle cells through suppression of the muscle developmental factor MyoD. This function seems to ensure there will always be a pool of stem cells for muscle repair and regeneration.

Adapted from the Delbrück Center for Molecular Medicine -
Berlin-Buch announcement.

Neural Stem Cells Regenerate Relay Circuits; New Axons Formed Across Severe Spinal Cord Injury

Interesting in light of the spinal cord neural stem cell human trials being planned by Neuralstem (CUR) and currently underway by StemCells Inc. (STEM). 

In the new University research, scientists were able to regenerate “an astonishing degree” of axonal growth at the site of severe spinal cord injury in rats.  Their research revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system (CNS).

The study also proved that at least some types of adult CNS axons can overcome a normally inhibitory growth environment to grow over long distances.  Importantly, stem cells across species exhibit these properties.

Researchers embedded neural stem cells in a matrix of fibrin -- a protein key to blood clotting already used in human neuron procedures -- mixed with growth factors to form a gel.  The gel was then applied to the injury site in rats with completely severed spinal cords.

Neuralstem Reports Positive Pre-Clinical Test Results With Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury

On the news, Neuraltem's market capitalization began the trading day at $54M and ended at approximately $74 million after reaching $105M midday. After close of market, the company released a statement of its intention to carry out a public offering of shares.

In the study, rats with surgically transected spinal cords, which rendered them permanently and completely paraplegic, were transplanted with Neuralstem's spinal cord stem cells (NSI-566).

Neuralstem reports that the animals recovered significant locomotor function, regaining movement in all lower extremity joints, and that the transplanted neural stem cells turned into neurons which grew a "remarkable" number of axons that extended for "very long distances" over 17 spinal segments, making connections both above and below the point of severance. These axons reached up to the cervical region (C4) and down to the lumbar region (L1). They also appeared to make reciprocal synaptic connectivity with the host rat spinal cord neurons in the gray matter for several segments below the injury.

Re-transecting the spinal cord immediately above the graft abolished the functional gain, indicating that the regeneration of host axons into the human stem cell graft was responsible for the functional recovery.

The cells that Neuralstem contributed to the study, NSI-566, are the same cells used in the recently completed Phase 1 clinical trial for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).  Neuralstem has also submitted an application to the FDA for a trial to treat chronic spinal cord injury with these cells.

Adapted from the Neuralstem announcement.

Cardiac Stem Sells From Babies Superior To Adult Stem Cells In Regenerative Ability

New research has found that cardiac stem cells (CSCs) from newborns have a three-fold ability to restore heart function to nearly normal levels compared with adult CSCs. Further, in animal models of heart attack, hearts treated with neonatal stem cells pumped stronger than those given adult cells.

To conduct the study, researchers obtained a small amount of heart tissue during normal cardiac surgery from 43 neonates and 13 adults. The cells were expanded in a growth medium yielding millions of cells. The researchers developed a consistent way to isolate and grow neonatal stem cells from as little as 20 milligrams of heart tissue. Adult and neonate stem cell activity was observed both in the laboratory and in animal models. In addition, the animal models were compared to controls that were not given the stem cells. 

"The surprising finding is that the cells from neonates are extremely regenerative and perform better than adult stem cells," said, Sunjay Kaushal, M.D., Ph.D., associate professor of surgery at the University of Maryland School of Medicine and director, pediatric cardiac surgery at the University of Maryland Medical Center. "We are extremely excited and hopeful that this new cell-based therapy can play an important role in the treatment of children with congenital heart disease, many of whom don't have other options."

Dr. Kaushal says it is not clear why the neonatal stem cells performed so well. One explanation hinges on sheer numbers: there are many more stem cells in a baby's heart than in the adult heart. Another explanation: neonate-derived cells release more growth factors that trigger blood vessel development and/or preservation than adult cells.

Adapted from the University of Maryland School of Medicine announcement.

Lighting Up Stem Cell Transformation Into Function-Specific Cells

A novel set of custom-designed “molecular beacons” allows scientists to monitor gene expression in living populations of stem cells as they turn into a specific tissue in real-time. The technology provides tissue engineers with a potentially powerful tool to discover what it may take to make stem cells transform into desired tissue cells more often and more quickly.

The researchers designed their beacons to fluoresce when they bind to mRNA from three specific genes in fat-derived stem cells that are expressed only when the stem cells are transforming into bone cells.

Over a three week period the team watched the populations for the fluorescence of the beacons to see how many stem cells within each population were becoming bone and the timing of each gene expression milestone.

The beacons’ fluorescence made it easy to see a distinct pattern in that timing. Expression of the gene ALPL peaked first in more than 90 percent of induced stem cells on day four, followed by about 85 percent expressing the gene COL1A1 on day 14. The last few days of the experiments saw an unmistakably sharp rise in expression of the gene BGLAP in more than 80 percent of the induced stem cells.

Each successive episode of gene expression ramped up from zero to the peak more quickly, the researchers noted, leading to a new hypothesis that the pace of the stem cell transformation, or “differentiation” in stem cell parlance, may become more synchronized in a population over time.

“If you could find a way to get them on this track earlier, you could get the differentiation faster,” said Eric Darling, assistant professor of biology in the Department of Molecular Pharmacology, Physiology, and Biotechnology at Brown University.

Adapted from the Brown University announcement.

Stem Cell Sector, Neuralstem's (CUR), Short Term Bet On A Molecular Cure For Depression

Neuralstem's technology enables the isolation and large-scale expansion of human neural stem cells from the developing human brain and spinal cord. In addition, the company has developed and patented a series of small molecule compounds -- low molecular weight organic compounds which can efficiently cross the blood/brain barrier -- they are wagering will stimulate the growth of new neurons in the hippocampus and provide a treatment for depression. If they're right, they and their shareholders win big. If they're wrong they'll be in the market for capital and they'll be there with less leverage than they have now.

The company has also developed a Spinal Cord Delivery Platform and Floating Cannula that has been demonstrated to deliver therapeutic agents to the spinal cord safely and effectively, a technology they have just licensed to Salt Lake City-based Q Therapeutics.

Nueralstem's recent venture into the capital markets was small, notable only for the low price of the offering. In mid-April Nueralstem (CUR) sold at $1.07 the day they announced the retirement of their CFO. In the following four months, which included announcements that additional patients had been dosed in their ALS clinical trial, that the first patient had been treated in their depression trial, the beginning of Zack's coverage of the firm with an 'Outperform' rating, and the receipt of a patent on the "Transplantation of Human Neural Cells for Treatment of

Patient Suffering From Long Standing Pancytopenia After Stem Cell Transplant Reportedly Treated Successfully With Pluristem Placental eXpanded (PLX) Cells Under Israeli Compassionate Use Policy

A 45 year old male, diagnosed with Acute Myeloid Leukemia (AML), a form of blood cancer, underwent chemotherapy to treat the cancerous cells. Treatments with chemotherapy remove cancerous cells as well as normal cells in the bone marrow, leaving the patient needing bone marrow transplantation. The patient received an unrelated (allogeneic) bone marrow transplant. However, he suffered from severe and long standing pancytopenia with associated complications after receiving hematopoietic stem cell transplantations.

Due to the patient’s major life threatening condition, 144 days post bone marrow transplantation, PLX cells were injected intramuscularly (IM) at a dose of 600x106 cells, divided into two administrations, one week apart, under compassionate use treatment. No local or systemic side effects were observed. In addition, the patient’s general clinical condition and well being significantly improved, resulting in his release from Hadassah Medical Center.

We are not told in the Pluristem announcement what 'general clinical condition and well being significantly improved' means except for the following statement:

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

Researchers Uncover Missing Link Between Blood Stem Cells And Cells Of The Human Immune System

The research was done using human bone marrow, which contains all the stem cells that produce blood during post-natal life.

"We felt it was especially important to do these studies using human bone marrow, as most research into the development of the immune system has used mouse bone marrow," said Dr. Gay Crooks, co-director of UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of post-natal life."

Prior to this study researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce cells in intermediate stages of development called progenitors, which make various blood lineages, like red blood cells or platelets. 

Stem Cells, Bioscaffolds, and Articular Cartilage Repair

Interesting look at an approach to creating and repairing cartilage from the Trinity College Dublin. Following the first video is a second that provides a broad and historical perspective on the development of cartilage repair. The second video is provided by a private company but the interviewee is Prof. Christoph Erggelet, an orthopaedic surgeon in Zurich/Switzerland affiliated with the Department for Orthopeadic Surgery and Traumatology, University Medical Center, University of Freiburg/Germany.

 

 

 

Astrocytes Control Generation Of New Neurons From Neural Stem Cells

New research has shown how astrocytes control the generation of new neurons in the brain. Earlier research in the same laboratory demonstrated that astrocytes reduce brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

“In the brain, astrocytes control how many new neurons are formed from neural stem cells and survive to integrate into the existing neuronal networks, said Milos Pekny, Professor and Laboratory Director, Center for Brain Repair and Rehabilitation, Dept. of Clinical Neuroscience and Rehabilitation, University of Gothenburg. "Astrocytes do this by secreting specific molecules but also by much less understood direct cell-cell interactions with stem cells.”

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

Transplanted Heart Muscle Cells, Derived From Embryonic Stem Cells, Electrically Couple And Beat In Sync With The Heart's Own Muscle

“These results provide strong evidence that human cardiac muscle cell grafts meet physiological criteria for true heart regeneration," said Dr. Michael Laflamme, University of Washington associate professor of pathology and member of the UW Center for Cardiovascular Biology and the Institute for Stem Cell & Regenerative Medicine.. "This supports the continued development of human embryonic stem cell-based heart therapies for both mechanical and electrical repair of the heart.”

In this study, the guinea pigs’ hearts had an injury to the left ventricle, the thick walled lower chamber in the heart that pumps oxygenated blood to the body. The injury left a scar and thinned the ventricle, which showed both reduced pump function and greater susceptibility to arrhythmias. Injured hearts that received the human cardiac muscle cell grafts showed partial re-muscularization of the scarred left ventricle.

“We showed a couple years ago that transplanting human embryonic stem cell-derived heart muscle cells improves the pumping activity of injured hearts,” said Dr. Laflamme,  “In this recent study we show that the transplantation of these cells also reduces the incidence of arrhythmias [heart rhythm disturbances].”