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Developing Human Embryonic Stem Cells for Grafting in Parkinson's Disease

机译:开发人胚胎干细胞用于帕金森病的移植

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Our own results suggest that a risk of teratoma formation inversely correlates with the duration of the in vitro differentiation protocol (Brederlau & Correia et al., 2006). While the yield of hESC-derived DA neurons is not a limiting factor of transplantation success anymore, the major problems associated with the actual application of hESC-based therapies for PD are associated with 1) poor survival of mature DA neurons and 2) risk of teratoma and tumor formation in the site of transplantation. The former is caused by the presence of residual undifferentiated/mitotic cells amongst the transplanted cells. We have refined the in vitro differentiation protocol resulting in a balance of proliferation and differentiation in the cultures and yielding 3-D structures (Transplantable Units, TUs) suitable for transplantation without further dissociation. We have also refined the technique allowing rapid handling and reliable intracerebral delivery of TUs in model animals; resulting in an improved cell survival. Finally we have identified the substantia nigra pars compacta-specific factor Fibroblast growth factor 20 (FGF20) as a factor affecting both differentiation and proliferation of hESC-derived DA progenitors in a dose-dependant manner.

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