Researchers at the University of California, Davis campus have developed a method to enhance the efficiency of reprogramming a non-pluripotent, somatic cell to a pluripotent stem cell. (more...)

A cornerstone of regenerative medicine is the study and use of pluripotent stem cells for the purpose of wound healing, tissue repair, and organ transplantation. Existing forms of pluripotent cells include embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. The ethical concerns and limited availability associated with ES cells, and the difficulties in generating large quantities of iPS cells underscore the necessity of finding additional sources of pluripotent cells. (more...)

Prostate cancer is one of the most common cancers to affect men and is the second leading cause of death amongst cancer victims. For decades, primary cultures of malignant prostatic cells have provided a convenient model system to study prostate cancer and tumorigenesis. However, these cell lines do not adequately recapitulate the microenvironment that supports tumor development in vivo. Many of the available prostate cancer cell lines (PC3, DU145, and LNCaP) are derived from metastases and are not inclusive of all prostate cancer phenotypes. Thus, there is a need for cell culture model systems that more effectively recapitulate the genetic and environmental composition of tumors. Seminal work carried out by Dr. Garraway's research group at UCLA has provided crucial insight into the development of a novel cell line derived from human fetal prostate tissue for the study of prostate tumors and tumorigenesis.       (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. There are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimer’s and Parkinson’s 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. In addition, cancer relapse has recently been attributed to the existence of cancer stem cells, which are resistant to traditional therapies, exist in numbers too small for detection, and have the potential to develop into new tumors. Treatments that target cancer stem cells would represent a great advance in the field of cancer medicine, and significantly improve prognosis and quality of life for patients by preventing relapse and metastasis. (more...)

Most human embryonic stem cell (hESC)-derived allografts are rejected within five years of transplantation even under chronic immune suppression. The current strategy to address the allograft rejection is to use immunosuppressants that systemically suppress the entire immune response, often increasing the risk for cancer and infection. Therefore there is an unmet need for specific immune suppression that prevents transplant rejection as well as reduces side effects. (more...)

Decellularized liver matrices have been successfully reconstituted with fetal or primary hepatocytes. Compositions of DLMs and methods for creating and use of DLMs are described. (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...)

Adipose stem cells (ASCs) can be used for the treatment of diabetes, insulin resistance, and obesity.  These cells can also be administered to increase the amount of brown fat thermogenesis (e.g., for treating obesity).  Mesenchymal stem cells (MSC) therapies are being developed for treatment of inflammatory, metabolic, cardiovascular, and degenerative diseases.  Both ASC- and MSC-based therapies are being developed for treating cancer, cardiovascular disease, acute lung failure, stimulation of tissue regeneration (e.g., skin, heart, and liver) and other degenerative and inflammatory conditions.  Currently, there are no established means for expanding ASCs or MSCs in vitro for extended periods of time in a non-differentiated state. (more...)

Compelling studies suggests that leukemia relapse occurs because standard chemotherapy fails to eradicate self-renewing leukemia stem cells (LSC), which may achieve therapeutic resistance via the cumulative effects of activating mutations in signaling pathways that promote self-renewal and survival within specific niches. One leukemia subtype, T cell acute lymphoblastic leukemia (T-ALL) is particularly prone to early systemic and isolated CNS relapse - often consequent to mutational activation of the NOTCH1 signaling pathway. These results suggested that identification and targeting of LSC within selective niches may abrogate the processes that culminate in the relapse of T-ALL. (more...)

Researchers at the University of California, Irvine have developed a novel method and device for cell separation that does not require cell labeling. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

COMP is an essential extracellular matrix protein that forms a “molecular bridge” between extracellular matrix components and provides a structure on which to bind.  The modular structure of COMP acts as a scaffold aggregating multiple growth factors and presenting them to the cell surface. In addition to binding multiple TGF-β1 molecules, COMP contains additional binding sites for growth factors and cytokines, including members of the VEGF, FGF, and HGF families. COMP’s cell surface binding properties bring the aggregate complex of COMP and associated growth factors to the cell surface preventing diffusion of the growth factors, increasing the physiological relevance of the signaling, especially where multiple signals are required, and ultimately increasing the growth-related transcription within the cell. (more...)

The global regenerative medicine market is expected to reach $1.4 Billion by 2015 with a largefocus on orthopedic applications. Bone loss occurs in a diverse growing population whichincludes cancer and dental patients, though most commonly associated with osteoporosispatients. Similar to any other living tissue, bone undergoes resorption and formation. In healthypatients these dynamic processes are balanced. When the rate of resporption increases orformation decreases bone loss occurs increasing the susceptibility to fractures. (more...)

The Dact2 protein may play an important role in oncogenesis, metastasis, wound healing and stem cell biology.  Molecular signaling pathways potentially involving Dact2 include the Wnt/b-catenin pathway, the Wnt/PCP non-b-catenin-dependent pathway, regulation of small GTPases of the Rho family, and pathways involving the Dishevelled signal transduction molecule, such as p120-catenin signaling.  There is evidence that Dact2 also regulates the TGF-b pathway.  In vitro and in vivo knockdown models would be very useful for studying Dact2 function in disease, but have not been reported to date. (more...)

Nanoscale and microscale topographies of biological tissues are important research tools for the study of cellular interactions and tissue engineering. Because many of the currently available fabricated topographies have simple and repetitive patterns of grooves or ridges, they do not mimic the physiological conditions of native tissue necessary for tissue engineering. A method that allows for formation of biomimetic tissue topographies will be an important advancement. Researchers at the University of California, Irvine have developed a simple, extremely rapid, and robust method to create well-controlled multi-scale (nano- and micro-) biomimetic grooves. The method is tunable such that grooves can be made in a variety of sizes that represent the physiological conditions of native tissues necessary for tissue engineering. In addition, this method is inexpensive and does not require large investment of capital equipment, specialized expertise, nor metal deposition. (more...)

Stem cells hold the promise of producing functional tissues that can replace those lost due to disease or injury. Stem cells exhibit "pluripotency," meaning that they have the potential to become any cell type in the body. New organ tissues, such as those found in the heart, liver, or nervous system, can be created from stem cells through the process of "differentiation." However, one major challenge in developing tissue replacement therapy is the heterogeneity and low yield associated with stem cell differentiation. It is well established that mechanical factors of the cellular microenvironment, including cell shape and density, influence stem cell differentiation and cell behaviors in general. Stem cells form isolated colonies in culture, and the geometry of these colonies can have a profound impact on their capacity for differentiation. There is currently a commercialized technology for controlling the size and shape of embryoid body formation and it has been shown that the size of embyroid bodies is important for differentiation. But many differentiation techniques do not involve the formation of embryoid bodies, and instead induce differentiation from 2D monolayer cultures of stem cells. Current 2D stem cell culturing protocols lack control over colony geometry because they allow for random attachment to tissue culturing surfaces. This leads to unpredictable stem cell growth which ultimately hurts our ability to successfully control the cell fate and differentiate into specific cell types. By patterning an extracellular matrix (ECM), such as Matrigel, colony formation, growth, and geometries can be highly regulated. By using silicone stencils a standard tissue culture plate can be converted into a cell patterning substrate while still using the normal ECM plating procedures. (more...)

A novel method for rapid and efficient differentiation of human embryonic stem cells into retinal pigmented epithelium. (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...)