News Article | December 7, 2016
CAMBRIDGE, MA -- Using LED lights flickering at a specific frequency, MIT researchers have shown that they can substantially reduce the beta amyloid plaques seen in Alzheimer's disease, in the visual cortex of mice. This treatment appears to work by inducing brain waves known as gamma oscillations, which the researchers discovered help the brain suppress beta amyloid production and invigorate cells responsible for destroying the plaques. Further research will be needed to determine if a similar approach could help Alzheimer's patients, says Li-Huei Tsai, the Picower Professor of Neuroscience, director of MIT's Picower Institute for Learning and Memory, and senior author of the study, which appears in the Dec. 7 online edition of Nature. "It's a big 'if,' because so many things have been shown to work in mice, only to fail in humans," Tsai says. "But if humans behave similarly to mice in response to this treatment, I would say the potential is just enormous, because it's so noninvasive, and it's so accessible." Tsai and Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the McGovern Institute for Brain Research, who is also an author of the Nature paper, have started a company called Cognito Therapeutics to pursue tests in humans. The paper's lead authors are graduate student Hannah Iaccarino and Media Lab research affiliate Annabelle Singer. "This important announcement may herald a breakthrough in the understanding and treatment of Alzheimer's disease, a terrible affliction affecting millions of people and their families around the world," says Michael Sipser, dean of MIT's School of Science. "Our MIT scientists have opened the door to an entirely new direction of research on this brain disorder and the mechanisms that may cause or prevent it. I find it extremely exciting." Alzheimer's disease, which affects more than 5 million people in the United States, is characterized by beta amyloid plaques that are suspected to be harmful to brain cells and to interfere with normal brain function. Previous studies have hinted that Alzheimer's patients also have impaired gamma oscillations. These brain waves, which range from 25 to 80 hertz (cycles per second), are believed to contribute to normal brain functions such as attention, perception, and memory. In a study of mice that were genetically programmed to develop Alzheimer's but did not yet show any plaque accumulation or behavioral symptoms, Tsai and her colleagues found impaired gamma oscillations during patterns of activity that are essential for learning and memory while running a maze. Next, the researchers stimulated gamma oscillations at 40 hertz in a brain region called the hippocampus, which is critical in memory formation and retrieval. These initial studies relied on a technique known as optogenetics, co-pioneered by Boyden, which allows scientists to control the activity of genetically modified neurons by shining light on them. Using this approach, the researchers stimulated certain brain cells known as interneurons, which then synchronize the gamma activity of excitatory neurons. After an hour of stimulation at 40 hertz, the researchers found a 40 to 50 percent reduction in the levels of beta amyloid proteins in the hippocampus. Stimulation at other frequencies, ranging from 20 to 80 hertz, did not produce this decline. Tsai and colleagues then began to wonder if less-invasive techniques might achieve the same effect. Tsai and Emery Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience, a member of the Picower Institute, and an author of the paper, came up with the idea of using an external stimulus -- in this case, light -- to drive gamma oscillations in the brain. The researchers built a simple device consisting of a strip of LEDs that can be programmed to flicker at different frequencies. Using this device, the researchers found that an hour of exposure to light flickering at 40 hertz enhanced gamma oscillations and reduced beta amyloid levels by half in the visual cortex of mice in the very early stages of Alzheimer's. However, the proteins returned to their original levels within 24 hours. The researchers then investigated whether a longer course of treatment could reduce amyloid plaques in mice with more advanced accumulation of amyloid plaques. After treating the mice for an hour a day for seven days, both plaques and free-floating amyloid were markedly reduced. The researchers are now trying to determine how long these effects last. Furthermore, the researchers found that gamma rhythms also reduced another hallmark of Alzheimer's disease: the abnormally modified Tau protein, which can form tangles in the brain. Tsai's lab is now studying whether light can drive gamma oscillations in brain regions beyond the visual cortex, and preliminary data suggest that this is possible. They are also investigating whether the reduction in amyloid plaques has any effects on the behavioral symptoms of their Alzheimer's mouse models, and whether this technique could affect other neurological disorders that involve impaired gamma oscillations. The researchers also performed studies to try to figure out how gamma oscillations exert their effects. They found that after gamma stimulation, the process for beta amyloid generation is less active. Gamma oscillations also improved the brain's ability to clear out beta amyloid proteins, which is normally the job of immune cells known as microglia. "They take up toxic materials and cell debris, clean up the environment, and keep neurons healthy," Tsai says. In Alzheimer's patients, microglia cells become very inflammatory and secrete toxic chemicals that make other brain cells more sick. However, when gamma oscillations were boosted in mice, their microglia underwent morphological changes and became more active in clearing away the beta amyloid proteins. "The bottom line is, enhancing gamma oscillations in the brain can do at least two things to reduced amyloid load. One is to reduce beta amyloid production from neurons. And second is to enhance the clearance of amyloids by microglia," Tsai says. The researchers also sequenced messenger RNA from the brains of the treated mice and found that hundreds of genes were over- or underexpressed, and they are now investigating the possible impact of those variations on Alzheimer's disease. The research was funded by the JPB Foundation, the Cameron Hayden Lord Foundation, a Barbara J. Weedon Fellowship, the New York Stem Cell Foundation Robertson Award, the National Institutes of Health, and the Belfer Neurodegeneration Consortium.
News Article | February 23, 2017
SALT LAKE CITY - Most kids say they love their mom and dad equally, but there are times when even the best prefers one parent over the other. The same can be said for how the body's cells treat our DNA instructions. It has long been thought that each copy - one inherited from mom and one from dad - is treated the same. A new study from scientists at the University of Utah School of Medicine shows that it is not uncommon for cells in the brain to preferentially activate one copy over the other. The finding breaks basic tenants of classic genetics and suggests new ways in which genetic mutations might cause brain disorders. In at least one region of the newborn mouse brain, the new research shows, inequality seems to be the norm. About 85 percent of genes in the dorsal raphe nucleus, known for secreting the mood-controlling chemical serotonin, differentially activate their maternal and paternal gene copies. Ten days later in the juvenile brain, the landscape shifts, with both copies being activated equally for all but 10 percent of genes. More than an oddity of the brain, the disparity also takes place at other sites in the body, including liver and muscle. It also occurs in humans. "We usually think of traits in terms of a whole person, or animal. We're finding that when we look at the level of cells, genetics is much more complicated than we thought," says Christopher Gregg, Ph.D., assistant professor of neurobiology and anatomy and senior author of the study which publishes online in Neuron on Feb. 23. "This new picture may help us understand brain disorders," he continues. Among genes regulated in this unorthodox way are risk factors for mental illness. In humans, a gene called DEAF1, implicated in autism and intellectual disability, shows preferential expression of one gene copy in multiple regions of the brain. A more comprehensive survey in primates, which acts as a proxy for humans, indicates the same is true for many other genes including some linked to Huntington's Disease, schizophrenia, attention deficit disorder, and bipoloar disorder. What the genetic imbalance could mean for our health remains to be determined, but preliminary results suggest that it could shape vulnerabilities to disease, explains Gregg. Normally, having two copies of a gene acts as a protective buffer in case one is defective. Activating a gene copy that is mutated and silencing the healthy copy - even temporarily - could be disruptive enough to cause trouble in specific cells. Supporting the idea, Gregg's lab found that some brain cells in transgenic mice preferentially activate mutated gene copies over healthy ones. "It has generally been assumed that there is correlation between both copies of a gene," says Elliott Ferris, a computer scientist who co-led the study with graduate student Wei-Chao Huang. Instead, they found something unexpected. "We developed novel methods for mining big data, and discovered something new," Huang explains. The investigators screened thousands of genes in their study, quantifying the relative levels of activation for each maternal and paternal gene copy and discovered that expression of the two is different for many genes. Surprised by what they saw, they developed statistical methods to rigorously test their validity and determined that they were not due to technical artifacts, nor genetic noise. Following up on their findings, they examined a subset of genes more closely, directly visualized imbalances between gene copies at the cellular level in the mouse and human brain. Results from Gregg and colleagues build on previous research, expanding on scenarios in which genes play favorites. Imprinted genes and X-linked genes are specific gene categories that differentially activate their maternal and paternal gene copies. Studies in cultured cells had also determined that some genes vary which copy they express. The results from this study, however, suggests that silencing one gene copy may be a way in which cells fine tune their genetic program at specific times during the lifecycle of the animal, or in discrete places. "Our new findings reveal a new landscape of diverse effects that shape the expression of maternal and paternal gene copies in the brain according to age, brain region, and tissue type," explains Gregg. "The implication is a new view of genetics, one that starts up close." The research was supported by the National Institutes of Health, Simons Foundation, University of Utah, and New York Stem Cell Foundation. In addition to Gregg, Huang, and Ferris, co-authors are Tong Cheng, Cornelia Stacher Horndli, Kelly Gleason, Carol Tamminga, Kenneth Boucher, and Jan Christian from the University of Utah, and Janice Wagner from Wake Forest School of Medicine. The study publishes in Neuron as "Diverse Non-Genetic Allele Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain".
News Article | December 18, 2015
Biomedical Engineering Professor Helen H. Lu has won a three-year $1.125 million Translational Research Award grant from the Department of Defense’s Congressionally Directed Medical Research Programs for her research on tendon-to-bone integration for rotator cuff repair. Lu is collaborating with William Levine, chairman and Frank E. Stinchfield Professor of Orthopedic Surgery at Columbia University Medical Center. The funding, part of the DoD’s Orthopaedic Research Program, will support preclinical trials to test the potential of a nanofiber-based device to enable biological healing between tendon and bone post rotator cuff surgery. “This is the culmination of our decade-long, interdisciplinary collaboration on integrative rotator cuff repair,” Lu said. “What is truly exciting is that the work planned in this new project will bring our novel technology another major step closer to clinical realization.” Rotator cuff tears represent the most common shoulder injury, with more than 600,000 repair procedures performed annually in the U.S. Among military personnel, the incidence of shoulder injuries is more than twice that of the general population. The rotator cuff tendon-to-bone insertion is often the site of injury when the cuff tendon tears. Current repair aims to surgically reconnect the torn tendon to the humerus. However mechanical fixation of the tendon fail to promote its integration with bone, and this inability contributes significantly to the high re-tear rate following cuff surgery. “So there is a large unmet clinical demand for integrative technologies for rotator cuff repair,” Levine observes. To address this problem, Lu, Levine, and their students developed an innovative approach that centers on the regeneration of the tendon-to-bone interface through the design of a biomimetic nanofiber scaffold coupled with controlled stem cell differentiation. Current clinically available strategies, such as graft patches, provide initial stability to tendons, but ultimately they lack the mechanical integrity and structural make-up necessary for tendon-bone healing. These disadvantages have significantly limited their clinical use. In contrast, the bioinspired technology developed by Lu and Levine is based on organized nanofibers (aligned and parallel to each other) that enable the integrative repair of rotator cuff tears by targeting the regeneration of the layered tendon-to-bone interface. “Given that the predominant reason for repair failure and requisite revision surgery is the lack of functional tendon-to-bone integration, our new approach represents a paradigm shift and will improve how tendons are repaired clinically,” Levine notes. Building upon their projects funded by the National Institutes of Health, the New York Stem Cell Foundation, and Wallace H. Coulter-Columbia Partnership, the researchers are planning a series of studies in the DoD grant to expedite tendon-to-bone healing by using the scaffold to harness the regenerative potential of stem cells and growth factor delivery. Completion of these studies will accelerate the development of a new generation of soft tissue fixation devices for use in both sports medicine and the treatment of degenerative joint diseases, which, said Lu, is “great news for athletes and non-athletes alike. Being able to functionally integrate different tissues such as tendon and bone will lay the foundation for the formation of composite tissue systems and ultimately, pave the way for total limb regeneration.”
News Article | September 27, 2016
A major impediment to developing effective drugs is the heavy reliance on animal models to derive estimates of human efficacy, toxicity, tolerability and metabolism. Their use has been driven by tradition and regulatory guidelines as well as a technical limitation: the lack of suitable human tissues that mimic disease states. This situation is about to improve considerably. Cellular reprogramming, the conversion of adult cells to induced pluripotent stem cells (iPSCs), has become embedded in the scientist’s toolkit and the likelihood of developing human disease models of high predictive utility has dramatically increased. As we enter an “Era of Reprogramming,” cell repositories are beginning to collect large numbers of patient-derived iPSC lines. While this is welcome news to drug hunters and basic researchers, the usefulness of these collections will depend on their quality. Animal models are a frustratingly imperfect method for studying complex human disorders and relying excessively on these models can lead to costly failures in the clinic. Human genetic studies have been highly successful in identifying genomic regions or genes that are statistically likely to contribute to disease. But translating those genetic findings into worthwhile drug targets has often proved elusive due to a lack of human tissue for study. Most human cells types are only available as transformed cell lines or from cadavers- sources that are far from ideal. Transformed cell lines have the advantage of immortality, but continuous passage introduces chromosomal abnormalities and changes in gene expression. Cadaveric tissues represent “one-off” samples that vary between donors due to various differences. An exciting solution to this dilemma arrived a decade ago in the form of cellular reprogramming. Reprogramming allows for the conversion of adult somatic cells to pluripotent stem cells by the forced expression of a small number of genes. Developed by Dr. Shinya Yamanaka in 2006 using mouse fibroblasts and extended to human cells by Yamanaka and Dr. James Thomson in 2007, cellular reprogramming allows for the creation of stem cell lines, called induced pluripotent stem cells (iPSCs), from individuals with defined diseases or genetic background. iPSCs share many properties with embryonic stem cells, most importantly the ability to be differentiated into a variety of somatic cell types important for drug discovery. Scientists immediately seized on reprogramming’s potential to develop in vitro models that could be used to understand disease biology and to test new drugs for efficacy or toxicity. Several funding agencies, such as the US National Institutes of Health, the California Institute for Regenerative Medicine, the Innovative Medicines Initiative and the New York Stem Cell Foundation, have begun to establish banks of iPSC lines with the goal of making them available to researchers. This effort on the part of funding agencies does not come without challenges. In particular, it is important to remember that if these lines are to increase our understanding of disease or accelerate the development of new drugs the quantity of available cell lines is less important than the quality of available cell lines. Several challenges still remain in the development of high quality iPSC banks. For iPSC lines to be most useful, they must be annotated with comprehensive medical data to allow selection of appropriate samples for study. Due to the costs of data collection, most clinical information will represent only a snapshot in time. In these cases, the clinical information should be as comprehensive as possible. However, where possible, funding agencies should strive to enable longitudinal data collection from donors. For example, knowing whether a donor’s disease stabilized or progressed, or whether it responded to drug treatment, is valuable data for interpreting results from iPSC-based models. Some researchers who recruit, evaluate and treat potential donors may have a vested interest in releasing as little clinical data as possible until after they’ve been published. This is an unfortunate reality of the present-day practice of science and cell banks may need to compromise on what information they request from depositors. Banks should strive to capture a broad swath of the population, including both patient cases and controls. Specific genetic information is crucial, especially for genes involved in drug metabolism, known toxicology sensitizers, and disease-causing/protective alleles. The cost in time and money to purchasing, differentiating and studying iPSC lines makes careful selection critical. In some cases, disease-specific lines, with no knowledge of genetic differences, will be acceptable. However, many researchers are focused on specific genes or pathways. They will want to know which lines have allelic differences in their genes of interest before choosing ones for study. Genetic information also provides the basis for developing companion diagnostics. As the cost of sequencing drops, the number of fully sequenced lines will increase, enhancing the value of such collections. In order to extract the most value from banks of patient-derived iPSC lines, informed consent should allow for their broadest possible use, including those that do not yet exist, so long as they conform to the spirit of the consent, and contribute to the understanding of disease and advancement of medicine. This includes allowing lines to be used by commercial entities for use in drug screening or commercial development. Care must be taken to ensure that consents conform to local legal requirements as regards patient confidentialtyconfidentiality, payment, and withdrawal. Nothing else discussed in this article will matter if customers refuse to purchase lines because donors were improperly consented. It is a good practice to screen donors for common infectious diseases, especially those caused by viruses that integrate into the genome. Even if retention of these infectious agents may not affect reprogramming and differentiation, disqualifying infected donors reduces one potential source of variability in iPSC function. It will be impossible for any single bank to control all iPSC lines. Therefore, banks should strive to develop a set of agreed-upon quality control assays for identity, pluripotency, sterility and chromosomal integrity. In addition, they should develop and validate methods that are faster and cheaper than G-banding for chromosomal integrity. As these issues with cell banks designed for research applications are addressed, immense potential will be unlocked for drug development. Additional issues, including production of cell lines under Good Manufacturing Practices, are required for cell banks designed for therapeutic applications.
News Article | August 22, 2016
Cells contain thousands of messenger RNA molecules, which carry copies of DNA’s genetic instructions to the rest of the cell. MIT engineers have now developed a way to visualize these molecules in higher resolution than previously possible in intact tissues, allowing researchers to precisely map the location of RNA throughout cells. Key to the new technique is expanding the tissue before imaging it. By making the sample physically larger, it can be imaged with very high resolution using ordinary microscopes commonly found in research labs. “Now we can image RNA with great spatial precision, thanks to the expansion process, and we also can do it more easily in large intact tissues,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, a member of MIT’s Media Lab and McGovern Institute for Brain Research, and the senior author of a paper describing the technique in the July 4 issue of Nature Methods. Studying the distribution of RNA inside cells could help scientists learn more about how cells control their gene expression and could also allow them to investigate diseases thought to be caused by failure of RNA to move to the correct location. Boyden and colleagues first described the underlying technique, known as expansion microscopy (ExM), last year, when they used it to image proteins inside large samples of brain tissue. In a paper appearing in Nature Biotechnology on July 4, the MIT team has now presented a new version of the technology that employs off-the-shelf chemicals, making it easier for researchers to use. MIT graduate students Fei Chen and Asmamaw Wassie are the lead authors of the Nature Methods paper, and Chen and graduate student Paul Tillberg are the lead authors of the Nature Biotechnology paper. The original expansion microscopy technique is based on embedding tissue samples in a polymer that swells when water is added. This tissue enlargement allows researchers to obtain images with a resolution of around 70 nanometers, which was previously possible only with very specialized and expensive microscopes. However, that method posed some challenges because it requires generating a complicated chemical tag consisting of an antibody that targets a specific protein, linked to both a fluorescent dye and a chemical anchor that attaches the whole complex to a highly absorbent polymer known as polyacrylate. Once the targets are labeled, the researchers break down the proteins that hold the tissue sample together, allowing it to expand uniformly as the polyacrylate gel swells. In their new studies, to eliminate the need for custom-designed labels, the researchers used a different molecule to anchor the targets to the gel before digestion. This molecule, which the researchers dubbed AcX, is commercially available and therefore makes the process much simpler. AcX can be modified to anchor either proteins or RNA to the gel. In the Nature Biotechnology study, the researchers used it to anchor proteins, and they also showed that the technique works on tissue that has been previously labeled with either fluorescent antibodies or proteins such as green fluorescent protein (GFP). “This lets you use completely off-the-shelf parts, which means that it can integrate very easily into existing workflows,” Tillberg says. “We think that it’s going to lower the barrier significantly for people to use the technique compared to the original ExM.” Using this approach, it takes about an hour to scan a piece of tissue 500 by 500 by 200 microns, using a light sheet fluorescence microscope. The researchers showed that this technique works for many types of tissues, including brain, pancreas, lung, and spleen. In the Nature Methods paper, the researchers used the same kind of anchoring molecule but modified it to target RNA instead. All of the RNAs in the sample are anchored to the gel, so they stay in their original locations throughout the digestion and expansion process. After the tissue is expanded, the researchers label specific RNA molecules using a process known as fluorescence in situ hybridization (FISH), which was originally developed in the early 1980s and is widely used. This allows researchers to visualize the location of specific RNA molecules at high resolution, in three dimensions, in large tissue samples. This enhanced spatial precision could allow scientists to explore many questions about how RNA contributes to cellular function. For example, a longstanding question in neuroscience is how neurons rapidly change the strength of their connections to store new memories or skills. One hypothesis is that RNA molecules encoding proteins necessary for plasticity are stored in cell compartments close to the synapses, poised to be translated into proteins when needed. With the new system, it should be possible to determine exactly which RNA molecules are located near the synapses, waiting to be translated. “People have found hundreds of these locally translated RNAs, but it’s hard to know where exactly they are and what they’re doing,” Chen says. “This technique would be useful to study that.” Boyden’s lab is also interested in using this technology to trace the connections between neurons and to classify different subtypes of neurons based on which genes they are expressing. Paola Arlotta, a professor of stem cell and regenerative biology at Harvard University who was not involved in the research, describes the new technology as potentially revolutionary. “In complex tissues like the brain or tumors, there are so many different cell types. It’s hard to distinguish one type of cell from the next, or to tell where certain molecules of RNA would be expressed,” Arlotta says. “This technology is very enabling for a lot of biology that we’ve been waiting to do.” The research was funded by the Open Philanthropy Project, the New York Stem Cell Foundation Robertson Award, the National Institutes of Health, the National Science Foundation, and Jeremy and Joyce Wertheimer.
News Article | February 23, 2017
For over a century, scientists have thought that most of our cells express genes from both parents' chromosomes relatively equally throughout life. But the biology is more nuanced, say scientists who invented a screen to measure the activity of specific genes from both parents. In Neuron on February 23, the researchers report that in rodent, monkey, and human brains, it's not unusual for individual neurons or specific types of neurons to silence genes from one parent or the other. Surprisingly, the differential activation of maternal and paternal gene copies was observed most often in the developing brain, impacting about 85% of genes. Gradually, as the brain matures, neurons increasingly express both parents' genes equally. However, for at least 10% of genes, maternal and paternal copies continue to be differentially expressed in the adult brain, revealing that this imbalance exists throughout an organism's lifetime for many genes in the brain. "This story has its roots in understanding why we reproduce sexually--normally, having two copies of a gene acts as a protect buffer in case one is defective," says senior author Christopher Gregg (@GreggNeuroLab), a neurobiologist at the University of Utah School of Medicine and a New York Stem Cell Foundation Robertson Investigator. "Our findings suggest that periods when the healthy gene copy is turned off could be critical windows during which cells are particularly vulnerable to a mutation in the other copy." Often mutations causing mental illness are heterozygous, meaning that they impact just one gene copy, and the Gregg lab is now exploring whether the effects they uncovered could explain why the same gene can be associated with a wide range of mental illnesses, from autism to schizophrenia, and why different people experience variation in the severity of their symptoms or risk for disease. The study demonstrates that it is possible for some cells in the brain to predominately express a mutant copy of a gene while others don't. Scientists have known for decades that some specific classes of genes differentially activate their maternal and paternal copies in the brain; however, the study from Gregg's lab uncovered a new and vast landscape of effects in the brain that cause differences in the activation of maternal and paternal gene copies according to age, cell type, brain region, and tissue. The study also raises the possibility of yet undiscovered mechanisms for how cells decide which parent's genes to shut off. Currently, it's known that children can inherit epigenetic imprints on their genome from parents that communicate whether a gene should be expressed, and for females, each cell inactivates one X chromosome. Finding the mechanisms that cause the effects described in the Gregg lab's new study could lead to new therapeutic approaches that work by activating silent healthy gene copies in the brain. "The screens revealed a new landscape of effects on maternal and paternal gene copies in the brain that were not due to imprinting and not due to X inactivation but took on all kinds of different forms," Gregg says. "Some effects are age specific, some are stable after birth, some impact most brain cells, some are more cell specific, some involved antagonistic effects where the maternal gene would go up and the paternal gene would go down, while others took on a different pattern." Gregg and his team at the University of Utah, including co-first authors Wei-Chao Huang, a graduate student, and Elliott Ferris, a bioinformatician, are now focused on understanding how differences in parental gene expression shape brain functions and disease risk. And while they are specifically looking at brain cells and mental illness, the screen they developed, now available to the scientific community, could provide insights across many cell types. This work has been supported by the National Institutes of Health, a Simons Foundation Autism Research Initiative Explorer Award, a University of Utah Seed Grant, and a New York Stem Cell Foundation Robertson-Neuroscience Award. Neuron, Huang and Ferris et al.: "Diverse Non-Genetic Allele Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain" http://www.cell.com/neuron/fulltext/S0896-6273(17)30057-0 Neuron (@NeuroCellPress), published by Cell Press, is a bimonthly journal that has established itself as one of the most influential and relied upon journals in the field of neuroscience and one of the premier intellectual forums of the neuroscience community. It publishes interdisciplinary articles that integrate biophysical, cellular, developmental, and molecular approaches with a systems approach to sensory, motor, and higher-order cognitive functions. Visit: http://www. . To receive Cell Press media alerts, contact email@example.com.
Nestor M.W.,New York Stem Cell Foundation |
Noggle S.A.,New York Stem Cell Foundation
Stem Cell Research and Therapy | Year: 2013
The study of cell differentiation, embryonic development, and personalized regenerative medicine are all possible through the use of human stem cells. The propensity for these cells to differentiate into all three germ layers of the body with the potential to generate any cell type opens a number of promising avenues for studying human development and disease. One major hurdle to the development of high-throughput production of human stem cells for use in regenerative medicine has been standardization of pluripotency assays. In this review we discuss technologies currently being deployed to produce standardized, high-quality stem cells that can be scaled for high-throughput derivation and screening in regenerative medicine applications. We focus on assays for pluripotency using bioinformatics and gene expression profiling. We review a number of approaches that promise to improve unbiased prediction of utility of both human induced pluripotent stem cells and embryonic stem cells. © 2013 BioMed Central Ltd.
Columbia University and New York Stem Cell Foundation | Date: 2012-10-10
The present invention is based on the discovery that certain small molecules can relieve ER stress, leading to increased insulin production in beta cells and improved insulin secretion. Methods of treating a disease or disorder in a subject, wherein the disease or disorder is characterized by intracellular endoplasmic reticulum (ER) stress, by administering to the subject, an effective amount of a compound that is an ER stress reliever, are provided herein.
New York Stem Cell Foundation | Date: 2013-12-05
The present invention provides modified oocytes having a nuclear genome derived from a first oocyte and cytoplasm derived from a second oocyte from a different subject, and methods for making and using such modified oocytes. The methods and compositions of the present invention can be useful in a variety of settings including, but not limited to, in in vitro fertilization (IVF) procedures.
New York Stem Cell Foundation | Date: 2012-11-30
The invention provides an automated system for producing induced pluripotent stem cells (iPSCs) from adult somatic cells. Further, the system is used for producing differentiated adult cells from stem cells. The invention system is useful for isolating somatic cells from tissue samples, producing iPSC lines from adult differentiated cells by reprogramming such cells, identifying the pluripotent reprogrammed adult cells among other cells, and expanding and screening the identified reprogrammed cells.