Su Chun Zhang

..This is also a rational and realistic way of producing enriched populations of functional neurons and glia for pathological analyses as well as possible therapeutic applications...

..We propose that careful studies on neural differentiation from human ES cells may provide more immediate answers to clinically relevant problems, such as drug discovery, mechanisms of disease and stimulation of endogenous stem cells...

..Here I will concentrate on the donor side and discuss how recent advancement in stem cell technology offers hope for transplant therapy, with a focus on the potentials and hurdles of human embryonic stem cells as a sustainable source...

..No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair...

..Furthermore, FGF-ERK1/2-PARP-1 cascade regulated the expression of PAX6, a transcription determinant of human neuroectoderm. Together, we propose that FGF regulates hESC neural specification through the ERK1/2-PARP-1 signaling pathway...

..This 3-month differentiation protocol consistently yields OPCs of high purity capable of producing myelin sheaths in vivo...

..2. Thus, despite the conservation of a similar transcriptional network across vertebrates, human stem/progenitor cells may respond differently to those of other vertebrates to certain extrinsic factors...

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..This synthesis has led to our suggestions on issues for future design of neural differentiation protocols...

..Disclosure of potential conflicts of interest is found at the end of this article...

..These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation...

..This protocol has been shown equally effective in generating motor neurons from human induced pluropotent stem (iPS) cells...

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..This method generates robust populations of functionally diversified astrocytes with high efficiency...

..Identification of the primitive neuroepithelial cells permits efficient patterning of region-specific progenitors and neuronal subtypes such as midbrain dopaminergic neurons...

..These results provide a technical basis for regulation of gene expression in hESCs and derivatives in vitro and in vivo...

..Cautions should be taken to choose the optimal promoter when lentiviruses are used for genetic modification of human ES cells...

..Thus, the directed neural differentiation system with small molecules, even without further purification, will facilitate basic and translational studies using human motoneurons at a minimal cost...

..Thus, neural cells derived from hESC provide a useful model system to understand the development of alpha-synuclein-related pathologies and allow therapeutic drug screening...

..Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain...

..Such information will be instrumental in translating biological findings to therapeutic development...

..Here, we describe an efficient lentiviral vector mediated method to establish stable transgenic hESCs...

..Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo...

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..Blocking FGF signaling inhibited neural induction, but did not alter the phosphorylation of the linker region of Smad1, suggesting that FGF enhances human neural specification independently of BMP signaling...

..In particular, the primitive neuroepithelial cells generated by this protocol can be further induced into neuronal and glial cells with forebrain, mid/hind brain, and spinal cord identities and targeted transmitter phenotypes...

..Our data suggest that BRAF oncogene levels can regulate melanoma neuronal differentiation and tumor progression...

..These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells...

..Transplantation studies indicated that the extensively expanded oligosphere cells retained myelination capacity. The oligospheres thus provide a valuable source for experimental cell therapy studies...

..Thus the survival, proliferation and maturation of oligodendroglia are influenced by other cell types...

..The ability to generate such cells from the adult brain therefore opens an avenue to explore the potential of these cells for repairing myelin disorders in adulthood...

..Thus, this study indicates that microglial reaction is graded in chronic neurological disorders and suggests that MHC II expression marks a functional change of activated microglia...

..This finding represents a significant step toward personalized regenerative therapies...

..This pluripotent cell line will allow both in vitro and in vivo analysis of functional development as well as the integration capacity of neuronal populations for cell-replacement strategies...

..This strategy and the master cell lines allow for rapid production of transgenic hESC lines in ordinary laboratories...

..These results lay the foundation for future studies examining the functional development of human neurons and provide support for the potential application of human cells in restorative neuronal therapies...

..The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA...

..We discuss how grafts are identified and functional outcomes are measured. Finally, we briefly discuss the cells that have been successfully transplanted, which may be used in future clinical trials...

..In comparison with other methods, our protocol does not use feeder cells, has a minimum dependence on proteins (purmorphamine replacing SHH), has controllable adherent selection and is adaptable for scalable suspension culture...

..They may thus provide a renewable source of functional human DA neurons for drug screening and development of sustainable therapeutics for disorders affecting the DA system...

..Thus, stem cells find their most powerful use in chemical biology, which may ultimately lead to applications in regenerative medicine...

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..This review will focus on the potential of ESCs as a source of transplantable cells for use in cell replacement therapy...

..Thus, our system not only provides a source of synchronized neuroectodermal cells, but also offers a paradigm to dissect mechanisms of neural induction and cell lineage specification during early human development...

..Hence, minocycline likely modulates the function of reactive glia in vivo to promote the survival and myelination of transplanted oligodendroglial progenitors...

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..Understanding the molecular regulators in directing the fate of neural stem cells will significantly expand our ability to instigate regeneration of our aging and/or diseased brain. ..

..It will ultimately speed up the potential use of hESCs in regenerative medicine.. ..

..This study will lead to an optimized procedure for generating enriched or purified neural precursor cells, which will lay the groundwork for potential future use of human ES cells in the treatment of neurological injuries and diseases. ..

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..Information gained from these studies will be crucial in ultimately utilizing human ES cells to treat neurological illnesses including Parkinson?s disease. ..

..Understanding the molecular regulators in directing the fate of neural stem cells will significantly expand our ability to instigate regeneration of our aging and/or diseased brain. ..