Stem Cells to Repair Hearts
Fueling hopes of patients with heart damage, a 2001 Nature study showed regrowth of heart tissue in mice. Subsequently refuted, the results pointed researchers to different stem cell-based strategies to treat heart damage. The BBC provides an overview of these approaches--ranging from injecting stem cells to directly converting cells into heart muscle.
Scientists Model Rare Neurodegenerative Disease in a Dish
Scientists from UCLA have succeeded in modelling ataxia telangiectasia (A-T), a rare genetic disorder, in a dish. This neurodegenerative disease affects 1 in 100,000 worldwide, with symptoms that range from difficulty in controlling movement to delayed development. A-T patients are at increased risk for cancer, lung disease, and diabetes. Mouse models, while providing insight into A-T, fail to fully reflect all aspects of this disease. In this study, the scientists coaxed A-T patients' skin cells to become induced pluripotent stem (iPS) cells, which became the type of neurons affected by this disease. The team aims to use these cells to better understand the mechanisms of this disease and to test drug-like chemical compounds.
Read more about this study in Genetic Engineering & Biotechnology News >>
Major Advance For Stem Cell Treatments, Based on NYSCF Proof-of-Concept Research
Scientists report the successful creation of patient-specific human embryonic stem cells with just an egg cell and a skin sample through a technique called somatic cell nuclear transfer (SCNT). NYSCF celebrates this major advance for the field that we anticipate will lead to advancements in uncovering new disease mechanisms and to personalized treatments and cures for disease.
Researchers, including a group at NYSCF, have conducted research to transfer the gene-containing nucleus of an adult cell into an egg cell to generate an early-stage embryo, called a blastocyst, and then derive stem cell lines. In 2011, NYSCF scientists paved the way for this discovery and achieved the proof-of-concept: Dieter Egli, PhD, and his team derived the first-ever stem cell lines through this method, yet the cells were triploid, containing an extra set of chromosomes.
To generate stem cell lines with only two sets of chromosomes, Shoukhrat Mitalipov, PhD, and his team at the Oregon Health and Science University first optimized the SCNT protocol in nonhuman primate cells. Selecting previously successful techniques, the scientists promoted blastocyst development by exposing the egg cells to both an electrical pulse and caffeine. They procured several lines of nuclear transfer embryonic stem cells (NT-ESCs).
Then translated to human cells, the group extended their approach across several egg donors with skin cells taken from a patient with Leigh syndrome (a lethal mitochondrial disease). The resultant NT-ESCs were fully pluripotent, meaning that they could become any of the other cell types that compose the body, contained the correct chromosome count, and lacked mitochondrial DNA of the skin cells.
NT-ESCs confer several advantages over other pluripotent stem cell sources. They, unlike embryonic stem cells, are patient-specific, and they carry fewer, potentially dangerous genetic changes than induced pluripotent stem cells, or cells derived from other adult cell types like skin. Importantly for cell therapies, NT-ESCs can be employed irrespective of a donor’s mitochondrial DNA.
NYSCF, one of the only research institutes in the country involved in this line of research, looks forward to the potential this technique holds develop cures and treatments for patients suffering from diseases.
Read an article on this advance in Forbes >>
Read more in Bloomberg Businessweek >>
Read about this work in Time >>
Read a post on the importance of this advance on the CIRM blog >>
Girl Breathes On Own With Stem Cell Engineered Wind Pipe
A two and a half year old girl has become the youngest recipient of a bioengineered wind pipe, made from her own stem cells. Born without a trachea, she had relied on an tube to breathe. Clinicians and scientists engineered a biodegradable plastic implant, which was then seeded with her own bone marrow stem cells. Once tissue matured in a bioreactor, surgeons transplanted the trachea, enabling her to breathe on her own for the first time. While the procedure does not have FDA approval, the scientists remain optimistic that further successes could lead to widespread treatment.
Scientists Identify New Hormone that Boosts Insulin-Producing Cells
Led by Douglas Melton, PhD, Harvard Stem Cell Institute Principal Faculty member and NYSCF Medical Advisory Board Executive Committee member, a new Cell study identifies a hormone in mice that contributes to the rapid proliferation of insulin-producing beta cells. In diabetes, beta cells malfunction and/or die, leading to a decreased ability to process sugars. While the disease can be managed by insulin injections and changes in diet and lifestyle, patients are at risk for related complications. Betatrophin, also found in humans, could be a potential target for type 2 diabetes treatments.
Self-Assembling 3D Droplets Mimics Tissue
University of Oxford researchers report in Science self-assembling, tissue-like networks of water droplets. Fats enclose the water droplets akin to a cell’s own lipid bilayer. Deposited by a three-dimensional printer, this material may act as a biological scaffold to help grow or even replace human tissue.
Stem Cells Spur Tissue Vascularization
A key challenge facing tissue engineers has been providing tissue with blood flow. Now, a group of scientists at the University of Michigan have identified the source of previous failed attempts to encourage tissue vascularization with cells. The quality of injected cells appears to be tied to how well blood vessels branch off and grow. Adult stem cells with scaffolding material form more robust vessels than conventional cells. These findings appear in Tissue Engineering Part A.
Blood Cells Rejuvenated Through Stem Cell Techniques
“New blood” takes on a literal meaning as researchers report the rejuvenation of mouse blood cells in Blood. The Lund University scientists reprogrammed stem cells that produce blood, effectively cancelling-out age-related changes to these stem cells. Old blood-forming stem cells become less able to mature into blood and immune cells.
For a Smarter Mouse, Add Astrocytes
They’re not just support cells, astrocytes play an important role in memory and learning according to a new Cell Stem Cell study. Steven Goldman and colleagues derived neural progenitor cells from human induced pluripotent stem (iPS) cells and then transplanted these cells into the brains of newborn mice. While most of the cells remained immature, some developed into astrocytes. These brain-cell endowed mice demonstrated superior maze-solving skills and recognized objects in new locations compared to non-chimeric mice. This study could help clue in neuroscientists to the evolution of astrocytes and their role in the human brain.
An iPSC First: Cell Therapy to Treat Parkinsonian Monkeys
Moving toward personalized therapies, researchers report the successful, matched transplantation of autologous rhesus monkey induced pluripotent stem (iPS) cells back into the brain. These genetically engineered monkeys suffer from balance disturbances and display other symptoms similar to human Parkinson’s patients. Led by Su-Chun Zhang at the University of Wisconsin, the team derived neural progenitors from parkinsonian monkeys’ skin samples, and then allowed the cells to fully mature into the brain. Tagged with fluourescent markers, the transplanted cells differentiated into a spectrum of brain cells—astrocytes, dopaminergic neurons, among others. On a promising note, the transplanted cells elicited a minimal immune response and the monkeys showed no signs of cancer at six month follow-up according to this Cell Reports study.
Flexible Needle for Potential Cell Therapies
As stem cell research gets closer to the clinic, the delivery of cell therapies lags behind. To transplant stem cell-derived treatments a flexible and precise tool instrument is necessary. Neurosurgeon and stem cell scientist Daniel Kim have developed a bendable needle that can successfully inject cells, even electrodes, into the brains of mice. While human brains are more complex, the needle is compatible with MRIs and uses an advanced computer system to accurately deposit materials to the wanted site.
Gene Therapy and Stem Cell Technology Treat Rare Disease in Mice
Combining advances in gene therapy and stem cell technology, researchers report a potential treatment for a mouse model of Duchenne muscular dystrophy (DMD), a fatal genetic disease. Rita Perlgeiro with Michael Kyba and colleagues engineered mice with a mutation to the dystrophin and utrophin genes, much like human DMD counterparts. They then generated induced pluripotent stem (iPS) cell lines from mouse skin cells and employed a special gene-correcting tool called Sleeping Beauty Transposon to deliver the correct copy of the utrophin gene. Once integrated into the skin cells’ DNA, the researchers differentiated these cells into muscle cells for transplantation back into the DMD mice. Exceeding expectations, the iPS-derived muscle cells engrafted into disease sites and helped reduce symptoms of DMD.
In Japan, iPS Cell Therapy Fast-Tracked to Clinic
Induced pluripotent stem (iPS) cells are slated to enter a clinical study in Japan for the treatment of age-related macular degeneration. Massayo Takahashi, an opthamologist at RIKEN Center for Developmental Biology and leader of this project, plans to treat six patients who suffer from this degenerative eye disease that commonly leads to blindness. Takahashi and her team will derive iPS cells from the participants’ skin samples and generate replacement retinal cells for transplantation into the retina. While safety concerns linger and some scientists harbor reservations on efficacy, Japan’s regulatory scheme will likely enable the study to move forward. If this iPS cell therapy proves safe and effective, it could enter formal clinical trials and treat patients in the clinic soon.
Read more about this iPS cell study in Nature >>
Liver Stem Cells Identified, Have Therapeutic Effect in Mice
For the first time, researchers led by Hans Clevers and Markus Grompe have successfully identified liver stem cells from a mouse. Reported in Nature, the team worked off a hypothesis that a previously identified marker of small intestine and colon stem cells could also mark liver stem cells. They could thereby isolate these liver stem cells and expand them in culture. Upon transplantation of these cells into mice with cirrhosis, there was a moderate therapeutic benefit.
US Government to Back Brain Mapping Project
Every dollar invested in the Human Genome Project returned $140 to the US economy. Now, President Obama will unveil a similar, ambitious plan to map the human brain in March. A multi-institutional, cross-field effort will build on basic research to better understand the brain and related disease pathologies. The ultimate goal of the Human Brain Activity Map is to find better treatments and cures to degenerative neurological disease.
Stem Cells Provide Insight into ALS
Subtle yet important, the interactions between motor neurons with neighboring cell types contribute to the pathologies of ALS (or Lou Gehrig’s disease), specifically motor neuron death. Reported in Proceedings of the National Academy of Sciences, mutations to a gene called TDP-43, although rare, cause astrocyte cell death. While astrocyte cell death is associated with motor neuron death, they are not directly toxic. Siddharthan Chardan, who led the study, generated induced pluripotent stem cells from ALS patients to make this discovery.
Skin Cells Directly Converted to Neurons
It just takes the repression of one protein to directly transdifferentiate skin cells into functional neurons according to a new study in Cell. Xiang-Dong Fu with a team of UCSD and Wuhan University scientists demonstrated that micro-RNAs silence a protein, which is sufficient to convert adult skin cells into neuron-like cells. The researchers are hopeful that this technique could lead to new drugs to treat degenerative diseases.
Degradable Polymer May Help Repair Broken Bones
Make no bones about it: engineering a material to repair bone tissue is complex. A newly developed polymer that can be seeded with stem cells may help support damaged bone. Mark Bradley and colleagues describe this osteogenic material in Advanced Functional Materials. Next steps include demonstrating the feasibility of this polymer for the repair of bone damage.
Read more about this work in Wired >>
Skin Cells Transformed to Repair Multiple Sclerosis Damage
Multiple sclerosis, an autoimmune disease in which immune cells attack the fatty protective layer of myelin cells, may have a potential treatment. Through stem cell techniques, a team led by Steven Goldman report in Cell Stem Cell the generation of myelin cells from human skin cells. The researchers implanted these new myelin cells in the brains of young, myelin-deficient mice, which greatly increased mouse survival. However, the successful hypothetical transplantation of these cells in human multiple sclerosis patients does not eliminate the immune system’s siege on this cell type. An application of this therapy would likely have to complement other treatments or performed repeatedly.
Read more on this study on BBC >>
Pinpointed Taste Receptor Stem Cells Could Help Treat Sense Loss
Taste receptor cells have a quick turnover rate. Every 10-16 days, new cells replace the old; yet, pinpointing the replenishing stem cell source has eluded researchers. In a study published in Stem Cells, researchers found a marker that identifies these cells. Significantly, these stem cells could be re-activated following taste receptor loss in cancer patients or the elderly. Peihua Jiang led the investigation.
Fat to Fight Obesity: Stem Cell Study Shows How
Brown fat, commonly thought as long-term energy source for hibernating animals, also plays an important role in blood sugar regulation and day-to-day metabolism. Previous studies have demonstrated a positive association between brown fat and leanness; thereby, adding to a patient’s brown fat reserves could potentially treat obesity. A study in Cell Metabolism shows how skeletal muscle stem cells could develop into brown fat cells. In mice, the injection of a drug that reduces miRNA-133 levels led to increased brown fat and leanness. Michael Rudnicki and colleagues are optimistic that this treatment could become a viable therapy to fight against the current obesity epidemic.
3D Printer Deposits Stem Cells
A new 3D printer technology deposits human embryonic stem cells in droplets. Building on 3D printer technology, this new platform can eject these fragile cells, which could help one day grow complex tissues. A Biofabrication study details an initial investigation of this printer’s capabilities. .
Hormone Prevents Stem Cell Death Following Lethal Radiation Dose
Radiation exposure often triggers cell death in hematopoetic, or blood-forming, stem cells. A study in Nature Medicine shows that the addition of a hormone following exposure could help prevent the loss of these essential progenitors. Co-authors David Kirsch and John Chute launched their investigation with genetically engineered mice that lacked genes to regulate death of endothelial (or blood vessel lining) cells. When exposed to radiation, these mice fared better than their wild type counterparts, and, notably, these former mice expressed high levels of epidermal growth factor (EGF). The team then fortified bone marrow transplants with EGF. Those mice that received the solution survived at a high rate following a lethal radiation exposure. Potentially, this research could be translated to humans as a therapy following accidental radiation exposure or radiotherapy for cancer.
Cell Therapy Treats Gastrointestinal Disorder in Mice
A team led by Heather Young and John Furness has demonstrated a possible cell therapy to treat gastrointestinal motility disorders like Hirschsprung disease. For patients with these diseases, the nerves that signal the digestive system to contract are not present, and surgery is required to correct this deficit. As reported in The Journal of Clinical Investigation, the transplantation of neural progenitor from mouse embryos can migrate and proliferate to the nerve-less gut in a mouse model.
Tuberculosis, a "Wolf-in-Stem-Cell-Clothing"
Under the cover of a mesenchymal stem cell, the tuberculosis (TB) bacterium persists, even years after living asymptomatically. A new study in Science Translational Medicine provides evidence for this “wolf-in-stem-cell-clothing” model. Researchers led by Dean Felsher and Antonio Campos-Neto worked off the hunch of Bikul Das, first author on the study. Das spent years as a clinician in India, where he observed TB bacteria in bone marrow samples of patients. The researchers initially studied a mouse model of disease, finding that the TB bacterium hid in a stem cell niche, and expanded the investigation to patients in India, who showed signs of the bacteria in stem cells obtained from the bone marrow.
Read a press release on the study >>
Scientists Create First "Disease in a Dish Model" of Rare Heart Condition
Arrhythmogenic right ventricular dysplasia/cadiomyopathy is a rare, inherited, and currently untreatable condition, which is a common cause of sudden death in adolescents. Researchers led by Daniel Judge and Huei-Sheng Vincent Chen generated cardiomyocytes from patients suffering from this condition; however, at first, they were unable to observe the cellular-level features of the disease in these immature cells. They developed, as reported in Nature, a method to trigger signs of the adult disease by activating the cells’ metabolism, producing a “disease in a dish.”
Researchers Develop Test to Pinpoint Transition in Degenerative Eye Disease
Approximately 20% of patients diagnosed with dry age-related macular degeneration develop the wet form, which leads to irreversible eye damage and eventual blindness. While the dry form can be diagnosed during an eye exam, there is currently no test that identifies the conversion from dry to wet. Per past studies, endothelial progenitor cells (EPCs) are elevated in the blood stream when new blood vessels form, a mechanism of disease for wet ARMD. Sai Chavala and colleagues developed a blood test to identify EPC levels in wet and dry ARMD patients with automated rare cell analysis (ARCA). Their results reported in PLOSOne show that the ARCA test might predict this transition to wet ARMD in dry ARMD patients.
Allogenic Stem Cells Help Rats Recover from Stroke
Rats, immediately following an induced ischemic stroke, fared better when injected with allogenic mesenchymal stem cells than a placebo. While there was no evidence of stem cell proliferation at the infarct site, tests revealed increased cell proliferation and nearly normal behavioral function in the stem cell recipients, measured two weeks later. The study, led by Sebastian Cerdan and Exuperio Diez-Tejedor, was published in Stem Cell Research and Therapy.
Japanese Researchers Derive Kidney Tissue from Stem Cells
Japanese researchers led by Kenji Osafune report the successful generation of mesoderm kidney tissue from induced pluripotent stem cells. This particular tissue type—between a stem and an adult kidney cell—was used to grow part of a urinary tubule. While safety issues need to be addressed, this study in Nature Communications could lead to new therapies for kidney disease.
Researchers Target Metabolism of Leukemia Stem Cells
Often, leukemia lays dormant before re-emerging. Researchers believe that a resistive subpopulation of leukemia stem cells underlie our current difficulty in eradicating this blood cancer. A new study in Cell Stem Cell reveals that, uniquely, leukemia stem cells have a “slower” metabolism than other tumor cells. Researchers led by Craig T. Jordan, applied a drug to target these cells’ metabolic pathway, effectively disrupting their ability to harness energy. These results may provide a new path to creating more effective leukemia treatments.
Leprosy Bacteria Reprogram Schwann Cells into Stem Cells
It’s not just humans who can reprogram cells. The leprosy bacterium can infect and thereafter revert adult Schwann cells into stem-like cells. The infection is spread by differentiation of the stem-like cells into skeletal muscle cells and by infected macrophages that consume these reprogrammed cells. Anura Rambukkana led the study, with results reported in Cell.
Stem Cell Therapy Offers Hope to Spinal Muscular Atrophy Patients
Children born with spinal muscular atrophy (SMA) have a grim prognosis: most infants rarely see it to their second birthday. This debilitating, genetic disease has no cure; however, a study in Science and Translational Medicine demonstrates a possible stem cell therapy. Giacomo Comi and colleagues derived stem cell lines from skin samples of patients with SMA, and corrected a faulty genetic copy of the gene responsible for the disease. The researchers then reprogrammed these corrected cells into motor neurons. Transplanted in mice, the motor neurons improved disease phenotype and increased lifespan.
Biomaterial Acts as Stem Cell Scaffold, Promotes Cartilage Repair in Patients
Reported in Science and Translational Medicine, a light-activated hydrogel helps to repair damaged cartilage by acting as a scaffold for stem cells. Jennifer Elisseeff and collaborators modeled the activity of the gel in vitro, demonstrating cartilage tissue development. Following successful application of the hydrogel in a caprine (a goat-antelope) model, the group launched a pilot study to treat patients with cartilage damage to the medial femoral condyle, the lower part of the femur. Patients reported less pain, and imaging studies revealed healthy cartilage.
Damage Stalled, Stopped in Duchenne Muscular Dystrophy Mouse Model
Duchenne muscular dystrophy (DMD), a rare genetic disorder, leads to muscle death and the formation of scar tissue due to a mutant copy of the dystrophin gene. Average DMD life expectancy is 25. While no cure exists, recent stem cell work in a mouse model reveals a possible therapy. Researchers led by Suzanne Berry-Miller generated aorta-derived mesoangioblast stem cells and then injected the cells into the hearts of dystrophin-deficient mice. The results, reported in Science and Translational Medicine, showed treatment delayed or prevented cardiac muscle damage.
Stem Cells to Treat Fractures in France
Project REBORNE will commence clinical trials to help repair fractured bone in France. Following successful pre-clinical work and approval by the French Medicinal Agency, autologous mesenchymal stem cells in combination with a biomaterial will be transplanted into the fracture sites of 30 patients. Ultimately, the researchers hope to expand the study to other European centers to demonstrate the safety and tolerability of this intervention.
Drug Reverses Deafness in Mice
Hearing loss in mammals is thought irreversible: damage wrought to ear hair cells can lead to permanent deafness. A new study in Neuron from Albert Edge and colleagues uncovers a potential drug that regenerates ear hair cells. Previous research demonstrated that this compound could generate ear hair cells from stem cells, informing the decision of these researchers to apply the drug to the cochlea of deaf mice. Imaging and other analysis showed hearing recovery and the growth of new ear hair cells. This may be a promising therapeutic pathway to help deaf individuals.
No Difference in Immune Response for Embryonic and Induced Pluripotent Stem Cells
The results of a Nature study may quell long-held concerns over the safety of transplanted induced pluripotent stem (iPS) cells. In a 2011 investigation, transplanted autologous iPS cells instigated an immune response in mice, a roadblock for the development of iPS cell therapies. However, Masumi Abe and colleagues demonstrated no difference in immune response between mice injected with undifferentiated iPS cells or embryonic stem (ES) cells or, significantly, skin or bone-marrow cells derived from iPS or ES cells. Nevertheless, the study may be limited by its methods in generating the differentiated bone-marrow cells from chimeric embryos, a technique that would not apply to a clinical setting.
Read more about the study in Nature >>
ALS Mice Benefit from Neural Stem Cell Transplant per Meta-analysis Study
A meta-analysis of 11 studies reveals that undifferentiated, mulitpotent neural stem cells (NSC) from mice or humans may slow the onset and mitigate the symptoms of ALS in mice. From these studies, Evan Snyder and fellow researchers concluded that the efficacy of this intervention was mediated by a range of factors. Of note, the transplanted cells benefited native neurons to produce their own protective molecules.
SCOTUS Will Not Hear Appeal in Sherley v. Sebelius
The Supreme Court refused to hear an appeal from the plaintiff’s of Sherley v. Sebelius. Significantly, this marks the end of a years-long legal battle to challenge the NIH’s ability to create guidelines for federally funded human embryonic stem cell research.
Oxford Researchers Reverse Blindness in Mice
University of Oxford researchers report strides to reverse blindness in the Proceedings of the National Academy of Sciences. The group, led by Robert MacLaren, transplanted light-sensitive progenitor cells to mice with zero visual function, representing late-stage retinitis pigmentosa. Examination revealed formation of a light-sensitive photoreceptive layer as well as neural integration.
Cancer Gene Essential for Stem Cell Maintenance
BRCA1, a gene commonly known for its role in cancer, has been found to play an essential role in hair follicle cell maintenance. As reported in Genes and Development, Cedic Blanpain and colleagues showed that deletion of this genes leads to eventual hair follicle stem cell death. Other cell types in the epidermis continued to proliferate despite this gene's deletion.
Read more about the study here >>
HER-2 Positive Cancer Stem Cells Contribute to HER-2 Negative Breast Cancer
A paradox that finally explains why certain breast cancers respond to treatment has been uncovered by Jian Jian Li and colleagues. For HER-2 negative breast cancers, often treatments crafted for HER-2 positive patients prove effective. A new study in Clinical Cancer Research reports that a radiotherapy-resistant group of HER-2 positive cancer stem cells are present in HER-2 negative breast cancers. These findings may help to elucidate treatments.
New Method Directly Converts Heart Muscle to Pacemaker Cells
The expression of a single gene can directly convert heart muscle cells to cardiac pacemaker cells (i.e. SAN cells) both in an animal and a dish. An advantage over stem cell-derived pacemaker cells, the direct reprogramming method as outlined in a new Nature Biotechnology study eliminates risk of tumor growth. The Cedars-Sinai Heart Institute scientists led by Hee Cheol Cho, PhD, hope, in going forward with this research, that these cells could replace electronic pacemakers for patients with cardiovascular damage or disease.
Biomaterial Helps Repair Cornea, Treat Blindness
To treat corneal blindness, University of Sheffield researchers led by Frederik Claeyssens have engineered a biodegradable material with pockets to hold stem cells in place as they help repair damage. The material mirrors the natural environment of corneal cells, an advantage over current corneal transplants. Details on the novel material are published in Acta Biomaterialia.
StemBANCC to Speed Drug Discovery and Testing
Pharmaceutical companies and academic institutions, with European Union backing, are collaborating to produce a bank of 1,500 induced pluripotent stem cell lines. This StemBANCC project, to be managed by the University of Oxford, will collect skin or blood samples from 500 individuals and derive stem cells to make available for research and drug development.
Researchers Derive Stem Cells from Urine
In Nature Methods, a group of researchers led by Duanqing Pei reported the derivation of neural progenitor cells from urine. Easily procured, human excreta could be a viable source of patient-specific stem cell lines. The researchers generated neurons and grafted the cells into the brains of newborn mice, which implanted and did not form tumors.
British Researchers Develop an Efficient Method to Derive Patient-Specific Stem Cells
Induced pluripotent stem (iPS) cells derived from banked or even frozen blood samples present a practical and efficient platform to generate patient-specific cells. Researchers led by Professor Nicholas W. Morrell published in Stem Cells Translational Medicine, a proof-of-concept study. They isolated late-outgrowth endothelial progenitor cells from blood samples of both well donors and patients with hypertension, and then reprogrammed these cells into iPS cells.
Paralyzed Dogs Regain Some Coordination Following Stem Cell Based Therapy
Jasper, a dachshund, might not go on long walks, but he can stay in step on a treadmill with harness support after participation in a stem cell-based trial conducted by Wellcome Trust-MRC Stem Cell Institute researchers. Professor Robin Franklin and his team isolated olfactory ensheathing cells from the nasal cavity, which promote neuron replacement. These cells, after culture and expansion, were transplanted into the spinal chord injury site of half the study’s canine participants while the other half received a placebo injection. The cell dose group showed improved fore-hind coordination compared to the control dogs. Based off of this study, published in Brain, the researchers hope to have sufficient “proof of concept” to pursue similar studies.
An Oncogene Plays Key Role in Brain Development
To better understand genetic factors involved in brain development, researchers led by Tristan Bouschet and Pierre Vanderhaeghen examined mouse embryonic stem cells. When oncogene BCL6 was overexpressed, the stem cells differentiated into cortical neurons. To confirm the gene’s effect, the researchers engineered mice to lack BCL6, which subsequently resulted in smaller, nerve-diminished brains. The study is published in Nature Neuroscience.
Stem Cells May be More Genomically Stable Than Believed
Cell mosaicism—genetic variations between individual cells of a particular type—may account for genomic “instability” observed in induced pluripotent stem cell lines. Researchers led by Mark Gerstein and Flora M. Vaccarino sequenced the complete genomes of stem cells derived from fibroblasts, and found significant copy number variations (CNVs), which are unique genetic variants harbored in DNA. Consequently, these results beg the question of how diverse our own, individual cells are.
News link: http://medicalxpress.com/news/2012-11-insight-subtle-genomic-differences-cells.html
Stem Cell-Derived Neurons Integrate and Function in Rodent Brains
Generated neurons from human embryonic stem cells not only integrated into rodent model’s hippocampus but displayed and promoted electrical activity when optogenetically stimulated. These results may encourage cell replacement therapy for the treatment of neudegenerative disorders and brain/spinal injury. Stuart Lipton, MD, PhD, led the scientific team with results published in the Journal of Neuroscience.
Isolated Pancreas Stem Cells Can Become Beta Cells
Walter and Eliza Hall Institute researchers led by Leonard Harrison, DSc, identified and isolated stem cells from the pancreas, and they thenderived insulin-producing beta cells. While other groups have generated beta cells from pancreatic cells, this PLoSONE study underscores the regenerative potential of a patient’s own stem cells, which could potentially be harnessed to treat type 1 diabetes.
Read more about the study here >>
Colombian Alzheimer's Disease Study Reveals Changes to Brain Before Symptoms
A large, extended Colombian family gripped by early-onset Alzheimer’s disease has helped researchers led by Eric Reiman, MD, determine how early (and rapidly) changes to the brain occur, even before symptoms are evident. The studies published in Lancet Neurology tracked 5,000 individuals with a genetic mutation that drives the development of this disease. Brain scans, cognitive tests, spinal taps, and related evaluations revealed changes to the brain years before apparent cognitive changes or the formation of amyloid plaques. The researchers will enroll this cohort into experimental drug studies to see if the disease can be arrested or reversed.
Read more about the study on The New York Times >>
Scientists Remove Extra Chromosome in Down's Syndrome Stem Cells
Trisomic disorders like Down’s syndrome (DS) may be corrected per a study published in Cell Stem Cell. Li B. Li and fellow researchers generated induced pluripotent stem (iPS) cells from DS patient skin samples. They then targeted the extra chromosome and removed it from the affected cells. Compared to the trisomic DS cells, the disomic cells were not significantly different in their ability to differentiate into hematopoietic cells. Consequently, these cells may serve as a model for comparison to further understanding of DS.
First Induced Pluripotent Stem Cell Model of Rare Eye Disease
David Gamm, MD, PhD, and University of Wisconsin colleagues report the first induced pluripotent stem (iPS) cell model of Best disease, a rare, genetic disorder that leads to macular degeneration. The researchers derived iPS cell lines from skin samples of Best disease patients and their well relatives, which were then reprogrammed into retinal pigment epithelial cells. This study published in Human Molecular Genetics underscores the utility of this "disease in a dish" model to understand the mechanisms of macular degeneration.
Two Studies Reveal Possible Heart Attack Treatment with Mesenchymal Stem Cells
Two studies published in the Journal of the American Medical Association assess the efficacy and safety of mesenchymal stem cell (MSC) treatment on heart attack patients. Taken together, these independent early-stage clinical trial results are mixed. The TIME trial, led by Robert Simari, MD, examined the effects of autologous mononuclear cells (MNCs) on 120 recent heart attack patients. Those patients who received the therapy showed no benefit either three or seven days after their cardiac incident. However, the POSEIDON trial, led by Alan Heldman, MD, which followed 30 patients who had a heart attack in the more distant past, demonstrated benefit at one year follow-up in both allogenic and autologous MSC dose groups. While both studies have limitations, some researchers are cautiously optimistic that MSCs could help patients with ischemia and related cardiac disease.
Nobel Laureate Publishes Study on Cellular Pluripotency Mechanism
Nobel laureate John Gurdon, DPhil, and colleagues published an article in Epigenetics & Chromatin, which details an aspect of direct reprogramming of cells following nuclear transfer. The researchers transferred the nucleus of an adult mouse cell into a frog’s egg, and they attached fluorescent markers in order to observe the activity of histones and chromatin, proteins responsible for the activation of genes. Observation in real-time revealed the essential role histone H3 plays in the activation of a known gene involved in cellular pluripotency. This discovery implies manipulation of H3 may be effective to render a cell pluripotent.
Proteins Reprogram Cells to Pluripotent State
An alternative method to achieve cellular pluripotency, Stanford University School of Medicine researchers led by John Cooke, MD, PhD, uncovered an efficient way to reprogram cells using cell permeant proteins, eliminating need for a viral vector. The researchers posit a process of “transflammation” prompts the cell to make its genetic material available when an immune response is elicited, which also makes it vulnerable to changes that render the cell pluripotent. This study is published in Cell.
