The production, culture, and harvest of stem cells are essential components of cell-replacement therapies that hold great promise in treating a variety of human diseases. Current methods of propagating and fate specifying stem cells are hampered by slow cell growth and poor efficiency. The vast majority of stem cells often do not reach the desired cell type. Therefore, there is a need to develop more efficient culture and induction methods for stem cells. Such improvements hold a particularly great potential for advancing research and treatment of neurodegenerative disorders or neurological trauma, both of which lack effective therapies.      (more...)

Investigators at UCSF have developed a novel robust protocol for programing human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) in vitro. (more...)

Treatment of peripheral nerve injuries resulting in severed nerves are challenging. The current standard of care utilizes autogenous nerve grafts to bridge nerve gaps. Such procedures have limited success including suboptimal functional recovery and donor site morbidity. To address this clinical need, a novel method of nerve regeneration is described comprising adipose derived stem cells (ADSCs). (more...)

Stem cell based musculoskeletal tissue-engineering presents the unique opportunity to repair or replace dysfunctional cells in degenerating tissue. In this context, one goal of tissue engineering is to propagate stem cells that can then be reintroduced into the degenerating tissue to repair or replace dysfunctional cells, restore the physical and biochemical properties of the tissue, and re-establish normal function. In particular, mesenchymal stem cells (MSC) are useful in the treatment of musculoskeletal degenerative conditions such as degenerative disc disease and osteoarthritis.  MSCs are abundant, relatively easy to isolate, and can differentiate into a variety of cell types. However, the ischemic and inflammatory environment characteristic of injured tissues proves hostile for the direct introduction of MSCs, which often do not survive in this setting. While growth factors are commonly used to pre-differentiate MSCs into chondrocytes prior to their use, this can cause terminal differentiation and cell hypertrophy that leads to inferior extracellular matrix material properties. Instead, pellet culture systems are better suited for tissue engineering because they can mimic certain embryonic microenvironments that stimulate stable cell differentiation and better support the regenerative process.     (more...)

Over 5 million Americans currently suffer with congestive heart failure and despite aggressive medical therapies targeted to treat this disease; the outlook for these patients remains grim, with estimated mortalities of 33% and 50% at 1 and 5 years, respectively. Congestive heart failure (CHF) remains a significant unmet need in the global medical community. A treatment option for CHF by cellular transplantation of stem cells is a developing research area. This approach has been studied using fetal cardiomyocytes, adult skeletal muscle cells, autologous bone marrow-derived mesenchymal stem cells, cardiac progenitor (CP) cells, and cardiomyocytes derived from embryonic stem cells. However, current studies have yielded modest results in reducing infarct size and scar tissue. Furthermore, the necrotic/apoptotic loss of the vast majority of donor cells within days after transplantation is a major drawback.  (more...)

Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. In the United States alone, four million patients suffer from Alzheimer's disease (AD), one million from Parkinson's disease (PD), 350.000 from multiple sclerosis (MS), and 20.000 from amyotrophic lateral sclerosis (ALS). Worldwide, these incurable neurodegenerative diseases produce immeasurable societal strain as they afflict more than 20 million people. Stem cell transplantation has recently emerged as an attractive alternative option for fighting neurodegenerative diseases; the transplantation of embryonic-stem-cell-derived dopaminergic neurons has been shown to be efficient in restoring motor symptoms in conditions of dopamine deficiency. Recent studies have shown that fibroblasts can be trans-differentiated into functional neurons by ectopic expression of at least three neuronal lineage specific transcription factors. Neuronal differentiation is a well-studied paradigm as a consequence of transcription reprogramming. The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell lineage-specific transcription factors. Neuronal differentiation is subject to additional layers of control, such as regulated RNA processing. (more...)

Lentiviral vector and method to pre-select/sort anti-HIV gene transduced cells prior to clinical transplantation. (more...)

Diabetes is a significant public health problem with 346 million patients worldwide and a total healthcare cost between $376 and $672 billion. In 2007, $174 billion, or approximately 10% of the total national healthcare cost was attributed to diabetes and its complications such as heart disease, hypertension, blindness, and kidney and nervous system diseases. Of the 25.8 million Americans diagnosed in 2011, about 10% are Type 1 Diabetes and the rest are Type 2. Restoring pancreatic function in Type 1 diabetic patients will prevent many of the downstream costly complications that require kidney transplantation, and heart and eye surgery. However, pancreatic transplantations has had limited effectiveness due to organ rejection in patients. As various types of stems cells have been shown to restore organ functions in clinical trials, identifying and purifying pancreatic stem cells will represent a big step towards becoming a viable clinical solution that can replace pancreatic transplantation. (more...)

Embryonic stem cells (ESCs) offer attractive therapeutic alternatives for many diseases and conditions such as diabetes, Parkinson's disease, cancer therapy, and many others. However, teratoma formation of transplanted ESCs is a major concern that needs to be overcome before translating this technology into clinical reality. (more...)

The generation of human induced Pluripotent Stem (iPS) cells holds great promise for development of stem cell therapies to treat a wide range of human diseases. However, the generation of iPS cells in the absence of integrative DNA vectors remains problematic. UCSD researchers have developed a simple, iPS generation approach to express reprogramming factors. Introduction of the vector into human fibroblasts results in the efficient generation of iPS cells with all the hallmarks of stem cells, including cell surface markers, global gene expression profiles and in vivo pluripotency to differentiate into all three germ layers.    (more...)

Chronic Myeloid Leukemia (CML) is known to be associated with a chromosomal transposition that yields a constitutively active BCR-ABL "fusion" kinase and current therapies include kinase inhibitors (e.g., imatinib and dasatinib) that are designed to "turn off" the constitutive activation of the fusion kinase. However, these are marginally effective in the later, more aggressive stages of the disease. One cause of refractory disease appears to be the residence of cancer stem cells (CSC) in protected tumor niches where they exit the cell cycle and revert to a quiescent state, which does not respond to the standard line of care. Such cells are found to have an altered isoform expression profile, which may provide new means to attack stem cells that are refractory to first-line therapies. (more...)

The early (Chronic) form of Chronic Myeloid Leukemia (CML) is most commonly treated with Bcr-Abl tyrosine kinase inhibitors (e.g., imatinib and dasatinib). These drugs effectively counteract the constitutive activation of a BCR-ABL kinase, which derives from a chromosomal transposition of part of the BCR region of chromosome 22 to the ABL gene on chromosome 9. However, the Chronic phase of CML is followed by two progressively more aggressive phases and current therapies are marginally effective in the later Accelerated and Blast Crisis stages of the disease. To prevent and treat refractory forms of CML, there is a need for alternative means targeting molecular processes that fuel progression. (more...)

Stem cells are capable of both self-renewing and differentiating into more specialized cells. These two defining characteristics make stem cells a powerful tool for biological research, as they provide the potential to regenerate tissue in a living organism and grow organs in culture.Our ability to probe human stem cell fate has been hindered by the inability to create cellular microenvironments that provide a platform to spatially program stem cell fate.  The invention described here provides the cellular microenvironment required to  investigate the signaling molecules involved in the induction of stem cell fate.  (more...)

The extracellular matrix (ECM) plays important roles in influencing cellular behavior such as attachment, differentiation, and proliferation. However, in conventional culture and tissue engineering strategies, single proteins are frequently utilized, which fail to mimic the complex extracellular microenvironment seen in vivo. A need exists for improved compositions for culturing brain cells that mimics the complexity of natural brain extracellular matrix. (more...)

Despite recent advances in tissue engineering and regenerative medicine, ischemia related to cardiovascular disease results in the death of more than 100,000 amputations per year from peripheral artery disease (PAD) in the US alone.  Very few biomaterials have been examined and of those examined (e.g. fibrin, collagen, alginate, and Matrigel). None of these provide all the native components of the skeletal muscle extracellular matrix. Most are limited to improving growth factor and cell delivery. Currently no material meets all of the properties of an ideal scaffold, namely enhanced neovascularization to reduce the ischemic environment, better cell adhesion, survival, and maturation of endogenous or exogenously added cells. There is a need to develop improved compositions for minimally invasive tissue-engineered therapies for the treatment of critical limb ischemia. (more...)

Researchers at UCLA have developed a novel method for inducing dendritic cells (DCs) from monocytes. Compared to current methods, this innovation generates DCs with greater potency as antigen presenting cells for the activation of T cells. These potent DCs could be infused into cancer or infectious disease patients as part of a vaccine to enhance T cell activation. (more...)

Traditional chemotherapy may fail to achieve complete remission of cancers due to resistance of the underlying cancer stem cells (CSCs) to the therapeutic agents. It is now well accepted that to achieve greater efficacy there is a need to specifically target CSCs within a tumor cell population. Furthermore, understanding the self-renewal potential of these CSCs, as well as their susceptibility to drug treatment and the overall malignant potential of the cancer, are essential steps to more successful cancer therapy. (more...)

Cell adhesion is an essential function that mediates the physical interaction betweeen cells and their microenvironment and plays an important role in tissue formation.  Chemical control of cell adhesion allows for temporal and spatial manipulations of cell-cell and cell-surface interactions with high resolution for therapeutic and research purposes.  Recent reports show that cell-surface grafted nucleic acids can serve as adhesion molecules that have the benefits of minimal cross reactivity with endogenous cell-surface receptors and combinatorial encoding of interactions.  Cell surfaces can be modified with DNA either covalently or non-covalently through direct linkage of oligonucleotides to hydrophobic molecules such as lipids and steroids.  Current labeling approaches have several disadvantages, including manufacturing difficulties, inability to stably integrate into the cell surface under typical culture conditions, interfering with cellular function, and failure to display adhesive sequence at controlled distances from the cell surface. (more...)

UC Davis researchers from the NSF Center for Biophotonics and UC Davis Health System have developed a method of identifying and sorting cardiomyocytes derived from human pluripotent stem cells.  This method, based on second harmonic generation (SHG) - a nonlinear optical technique, does not require genetic modification of the cell or any exogenous labels to be used, which makes this an attractive technique for obtaining pure populations of cardiomyocytes under xeno- and vector- free conditions most appropriate for clinical and therapeutic use, as well for tissue engineering and drug discovery applications.There are currently no established methods for sorting pur populations of stem cell derived cardiomyocytes.  Methods that use fluorescent reporters require the introduction of a reporter vector and result in genetically modified cells, reducing their utility for clinical applications.  Other fluorescent-based staining methods have shown to be only applicable for selecting very mature cardiomyocytes.  Surface marker based methods require exposing human cells to products of animal origin, which may increase the risk of non-human pathogen transmission and render the cells unsuitable for clinical use.Second harmonic generation (SHG) is a laser-based technique that identifies stem cell derived cardiomyocytes based on the direct detection of myosin bundles, which generates a unique second harmonic signal when excited by intense laser pulses.  This signal is specific to the cardiomyocyte phenotype and is absent from undifferentiated stem cells and other non-cardiomyocyte cells that are found in the population following the directed differentiation of stem cells to the cardiac lineage.  SHG is able to discriminate cardionmyocytes at different stages of maturation/development, and can detect very immature cells.  When integrated into a flow cytometric configuration, non-invasive sorting for pure populations of stem cell derived cardiomyocytes is feasible. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

The recent identification of rare cell populations within tissues that are associated with specific biological behaviors, for example, progenitor cells, has illuminated a limitation of current technologies to study such adherent cells directly from primary tissues. The micropallet array is a recently developed technology designed to address this limitation by virtue of its capacity to isolate and recover single adherent cells on individual micropallets. The capacity to apply this technology to primary tissues and cells with restricted growth characteristics, particularly adhesion requirements, is critically dependent on the capacity to generate functional extracellular matrix (ECM) coatings. The discontinuous nature of the micropallet array surface provides specific constraints on the processes for generating the desired ECM coatings that are necessary to achieve the full functional capacity of the micropallet array. We have developed strategies, reported herein, to generate functional coatings with various ECM protein components: fibronectin, EHS tumor basement membrane extract, collagen, and laminin-5; confirmed by evaluation for rapid cellular adherence of four dissimilar cell types: fibroblast, breast epithelial, pancreatic epithelial, and myeloma. These findings are important for the dissemination and expanded use of micropallet arrays and similar microtechnologies requiring the integrated use of ECM protein coatings to promote cellular adherence. (GunnN.M., MS; Bachman M., Li G.P., Nelson E.L.Fabrication and biological evaluation of uniform extracellular matrix coatings on discontinuous photolithography generated micropallet arrays. J Biomed Mater Res A. 2010 Nov;95(2):401-12.) (more...)

Understanding the basic mechanisms of cognitive decline and how the subcellular organization of signaling molecules is altered with cognitive decline could potentially yield novel therapeutic targets for neuronal aging and neurodegeneration.Cholesterol is a major lipid component of synapses and a limiting factor in synapse activity. Age-related impairments in the biosynthesis, transport, or uptake of cholesterol by neurons in the CNS may adversely affect synaptic circuitry. Moreover, caveolin-1 (Cav-1), a cholesterol binding and resident protein of membrane lipid rafts (MLR; discrete regions of the plasma membrane enriched in cholesterol), organizes and targets synaptic components of the neurotransmitter and neurotrophic receptor signaling pathways to MLR. (more...)

In addition to their vast therapeutic potential in various neurological disorders, stem cells are also being developed for in vitro disease modeling and drug screening purposes. In vitro recapitulation of developmental differentiation processes permits the generation of specific neural cell types from pluripotent stem cell sources. For example, iPS cells from patients would allow the generation of patient-specific neural cell subtypes for disease modeling, target identification, drug screening and toxicity testing. Such approaches are anticipated to streamline drug development due to the use of more relevant human models instead of animal models.   While some cell types and sources have been identified as being potentially useful for these applications, their efficacy has not been proven and questions about their efficacy and safety still remain unanswered. Currently there is a need for advanced tools that would enable selection and generation of useful cell types for transplantation, and generation of cellular model systems for human diseases.   DESCRIPTION: UCSF investigators have discovered a highly efficient method of differentiating medial ganglionic eminence (MGE) cells from human iPS cells and embryonic stem cell sources. MGE cells are the precursors to forebrain inhibitory neurons that, when impaired, play a role in several diseases including epilepsy, Parkinson’s, Alzheimer’s, autism, schizophrenia, neuropathic pain and spasticity. The investigators’ prior work has shown that MGE cells possess several advantageous properties that would make them useful for treating neurological diseases, namely Parkinson’s disease and epilepsy, see references 1-8, below.   Recently, they have devised a robust method for generating MGE cells from iPS cell sources or embryonic stem cell sources, which consists of simple steps that do not require genetic engineering. The yield is close to 100% efficiency, which is a ten-fold improvement over currently available methods.   Ongoing work is focused on testing therapeutic efficacy of iPS-derived MGE cells in several animal disease models.  (more...)

Somatic cells can be induced to generate pluripotent stem cells that functionally resemble embryonic stem cells (ES cells). This reprogramming process, rooted in the remarkable cellular plasticity retained during differentiation, can be triggered by exogenous expression of a set of ES-cell specific gene regulators. However, reprogramming occurs with low efficiency and slow kinetics using the current technologies, reflecting our lack of in-depth mechanistic understanding of this process. At present, among the best-characterized reprogramming factors are a defined set of transcriptional regulators, Oct4 and Sox2, Klf4 and c-Myc. Most of these factors constitute integral components of the core gene regulatory circuits that coordinately control pluripotency and self-renewal in pluripotent stem cells.  miRNAs are a large family of small non-coding RNAs that primarily repress gene expression by pairing with partially complementary mRNA targets. The small size of miRNAs, combined with their imperfect target recognition, gives them enormous capacity and versatility to regulate global gene expression. This technology describes how specific miRNAs can be used to reprogram cells to generate pluripotent stem cells.   (more...)

Embryonic stem cells are used for producing a number of cell types in vitro, including endothelial cells, vascular progenitor cells, and hematopoietic cells. However, the derivation of these cell types from stem cell progenitors and their on-going maintenance often requires the use of serum-containing cell culture media, which can lead to batch variations and to contamination of the cells by unknown animal proteins or by other exogenous materials such as cytokines. (more...)

Researchers at UC Berkeley have developed a synthetic polymer interface for the long-term self-renewal of human embryonic stem cells (hESCs) in defined media. Current culture systems for hESCs require the use of isolated animal derived extracellular matrix proteins or mouse embryonic feeder cells. The proposed use of a completely synthetic cell culture substrate avoids the problems associated with the variability of and the exposure to animal products. The hydrogel network coating is comprised of aminopropylmethacrylamide (APMAAm) monomer and N,N-methylenebis(acrylamide) (bis) crosslinker that was grafted to standard tissue culture polystyrene (TCPS) dishes via photoinitiated addition polymerization. Results for hESC proliferation and pluripotency markers were both qualitatively and quantitatively similar to cells cultured on MatrigelÔ -coated substrates.   (more...)

UC San Diego researchers have optimized a bacterial artificial chromosome for high efficiency homologous recombination in human ES cells. This approach allows easy genetic manipulation of human ES cells. This technology can be used to genetically tag lineage-specific loci for identification and purification during the lineage-specific differentiation of human ES cells. (more...)

The host immune system is crucial to final resolution of viral infection. Unfortunately, many viruses, such as HIV-1 and hepatitis C virus (HCV), can evade the immune system. There is no pharmaceutical treatment that can eradicate these viruses from infected individuals. The fate of these infected individuals hinges on the findings of new therapeutic approaches, which has been a long-standing goal of HIV/AIDS research. (more...)

Urinary incontinence (UI) and stress urinary incontinence (SUI) are medical and social conditions that greatly erode ones quality of life.  These conditions are embarrassing and cause significant hospitalization. There is a great prevalence of UI in women of all ages (13 million), and approximately 50% of all incontinent women are classified as having SUI. SUI is caused by the loss of anatomic support and/or atrophy and dysfunction of the sphincteric mechanism of the urethra. This loss of support and/or atrophy then results in involuntary urine loss during any activity that causes abdominal straining (i.e. laughing, coughing, and sneezing). One of the current treatments for SUI involves injecting bulking materials into the urethral tissues. However, multiple injections are required, cure rates are low, and there are significant problems with material loss and migration. Treatments of bladder conditions and bladder substitution involve attempts at urinary tract reconstruction, using mature smooth muscle cells obtained from the host. The procurement process is morbid, and only small amounts of cells are obtained. Thus, there is a need for a better curative treatment that can improve the quality of life of these patients. (more...)

Neural stem cells offer great potential for treatment of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease; for treatment of neural dysfunctions such as dementia and epilepsy; and for repairing debilitating neural injuries such as brain traumas, spinal cord traumas, and strokes. However, adult stem cells for certain types of neural tissues are not available in sufficient quantities for commercial purposes. Embryonic stem cells may overcome this limitation, but growing neural cell types from them has been hampered by the difficulty in obtaining homogenous cell populations, in obtaining the glial cell subtype, and in obtaining a suitable culture media. Moreover, the full regeneration of neuron tissue requires the correct geometric orientation of neural cells, not just the growth and differentiation of stem cells into the required neural cell types. On a normal culture surface, a neuron cell grown in vitro will extend its axons in all directions, thereby failing to replicate the parallel, cell-to-cell orientation of axons found in vivo. At present, there are no simple and economical methods available for growing, differentiating, and correctly orienting embryonic stem cells to regenerate functional neurons. (more...)

Researchers at UC San Diego 's BioEngineering Department have recently developed a novel new dielectrophoretic (DEP) system for cell separation that will possess great advantages over state-of-the-art systems. Existing DEP technologies rely upon the difference in crossover AC frequencies between various cell populations to separate them into distinct groups. The technique becomes less effective as the cell types become more similar and the surrounding fluid becomes more complex (higher ionic strength), as in whole blood. This problem is overcome by the present invention, which will allow cell separation to be carried out under high ionic strength conditions.  (more...)

UC San Diego researchers have discovered a cardiac progenitor population that can be expanded and propagated in vitro. The undifferentiated cells express a characteristic subset of phenotypic markers, which allows the cells to be visualized and manipulated. These cells are capable of differentiating in vitro into more than one cell type when selected from mouse or rat hearts. (more...)

The N-myc family of genes play a crucial role in the human body and is required for the growth and development of multiple organs, including the heart. The overexpression and amplification of N-myc is associated with a variety of tumors, most notably neuroblastomas and other childhood tumors. Despite its clinical relevance, little, if anything, is known as to which genes control expression of N-myc in vivo. The technology presented here provides evidence that N-myc expression can be regulated with T-box transcription factors (Tbx). T-box refers to a group of transcription factors that are expressed in a wide variety of tissue types and are involved in the development of diverse organs and tissues, particularly in the limbs and the heart. T-box genes also regulate patterning and cell fate, cell survival, and/or proliferation. Mutations in T-box genes are the cause of several congenital diseases and are implicated in cancer. (more...)

Methods to identify individuals predisposed to the progression of cancer are paramount for its effective diagnosis and treatment, and for assessing disease progression. Recently, cancer-specific splicing and expression events in the Wnt/b-catenin signaling pathway have been associated with the progression of myelogenous leukemia. These cancer-specific events provide a focal point for investigating disease progression in leukemia and in other cancers. (more...)

Neural stem cells may be implanted at a region remote from neuron degeneration. This invention teaches a method of treating neurodegenerative disorders arising from the lack of cells that produce particular neurotransmitters in neural circuitry by transplanting exogenously cultured and expanded neural progenitors which, upon tranplantation into a neural tissue, differentiate into neurons capable of integrating and producing neurotransmitters to overcome the symptoms associated with the neurodegeneration. A patent application has been filed and published: PCT/US2005/041631. (more...)

Knowledge of DNA gene sequences and other parts of the genome of organisms has become indispensable when studying biological processes, diagnostic research, and forensic research. Following the development of dye-based sequencing methods with automated analysis, DNA sequencing has become easier and faster by a magnitude of orders. The prominent rapid high-throughput DNA sequencing methods include Genome Sequencer using pyrosequencing by Roche/454, SOliD technology by Applied Biosystems, and the sequencing by synthesis technology employed by Ilumina/Solexa. Methods for real-time direct sequencing from single DNA molecules are also emerging. These include the SMART technology being developed by Pacific Biosciences and the FRET-based sequencing method by VisiGen Biotechnologies (a part of Life Technologies Incorporated). The use of fluorescent-labeled nucleotides in almost all current single molecule-sequencing methods with optical imaging presents numerous problems, including background fluorescence and the requirement for a polymerase capable of incorporating labeled nucleotides. (more...)

Stem cell therapy holds the promise of treating a variety of human conditions such as diabetes, cancer, and neurological diseases. It is thought that stem cells could be especially useful for neurological diseases and disorders as the brain has a limited capacity for self-repair and regeneration. Additionally, there are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimers, Parkinsons, and Huntingtons disease. Collectively, these conditions represent a significant unmet medical need. Regenerative approaches for the brain have the potential to address the cause of the disease, rather than simply addressing symptoms, by repairing or reversing the disease state. However, because the underlying causes of the brain diseases are diverse, several different approaches are required to adequately address the various causes. Some examples include cell replacement for dead or lost cells, modification and augmentation of faulty circuitry, and delivery of therapeutics to poorly functioning cells for protection from degeneration. While some cell types and sources have been identified (e.g. fetal porcine ganglionic eminence cells and dopaminergic neurons), their efficacy has not been proven. In addition, questions remain about whether such cells will form brain tumors in vivo, persist for long periods of time, or will work in aged brains, when people are most susceptible to neurological disease. There is a need in the field for the identification of cell types that can be applied in many disease contexts. DESCRIPTION: UCSF Researchers have discovered that a population of neural precursors, called medial ganglionic eminence (MGE cells), possess several advantageous properties that would make them useful for a number of neurological diseases. When injected into various regions of the brain, MGE cells disperse homogenously over long distances, form inhibitory interneurons (GABAergic neurons), integrate to form functional connections with endogenous circuits, and influence the activity of surrounding neurons. Interestingly, MGE cells behave this way in postnatal brains, suggesting they could work in aged brains. By virtue of these qualities, it is thought that MGE cells can be used to treat several brain diseases via cell replacement, modification of endogenous circuitry, or by delivery of therapeutics. To support this assertion, the researchers have performed proof-of-principle experiments in rodent models of epilepsy and Parkinsons disease. Implantation of MGE cells into the cortex of postnatal brains in rodent models of epilepsy was shown to significantly reduce seizure symptoms. MGE cells achieved this via both GABAergic modulation of electrical activity and cellular replacement of inhibitory neurons. Further, implantation of MGE cells into the striatum of 6-OHDA rodents was shown to ameliorate symptoms of Parkinsons disease via modulation of faulty circuitry resulting from degeneration of dopaminergic input. Based on these initial data, the researchers envision that MGE cells could be applied to additional brain disorders. Indeed, preliminary data suggest that MGE cells could be used to treat diseases caused by aberrations in the organization or activity of the brain, such as stroke, cerebral palsy, and Schizophrenia. MGE cells can regulate a process known as experience-dependent plasticity, which allows for changes to be made in the wiring or activity of neurons. Selective reactivation of this process in the adult brain could result in functional reorganization that could fix or compensate for any lack of function and alleviate the symptoms of disease. Preliminary data also suggest that MGE cells can be used to treat spasticity caused by spinal cord injury. It is thought that spasticity results hyperactivity spinal circuitry. MGE cells grafted into the spinal cord are expected to integrate and produce factors that inhibit local circuitry to reduce spasticity. Experimental testing in related animal disease models is underway. (more...)

Improvement of Electrical and Contractile Properties in Human Embryonic Stem Cell-derived Cardiomyocytes  (more...)