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首页> 外文期刊>Stem cells translational medicine. >Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal‐Free Conditions
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Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal‐Free Conditions

机译:在粘附和无动物条件下对人类多能干细胞的高效神经转化

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Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal‐free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal‐free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. S tem C ells T ranslational M edicine 2017;6:1217–1226
机译:人类胚胎干细胞(hESCs)和诱导性多能干细胞(hiPSCs)的神经分化可以产生人类神经细胞亚型的宝贵而强大的来源,为神经发生和发展的研究以及治疗神经疾病具有广阔的前景。然而,当前的hESC和hiPSC的神经分化方案要求动物因素或类胚体形成,这降低了效率和产量,并强烈限制了医学应用。在这里,我们开发了一种简单,无动物的协议,用于在贴壁培养条件下对hESC和hiPSC进行神经转化。一个简单的包含胰岛素的中等配方可以诱导> 98%的hESCs和hiPSC直接转化为具有神经玫瑰花结特征的可扩展,可移植和功能性神经祖细胞。神经祖细胞进一步分化为多巴胺能和脊髓运动神经元以及星形胶质细胞和少突胶质细胞,表明这些神经祖细胞保留了对指示性信号的响应性,从而揭示了该方案在治疗不同神经退行性疾病中的强大适用性。该规程包括不含动物的培养基和人类细胞外基质成分,可避免类胚体,这一事实使该规程适用于临床。系统杂志翻译医学杂志,2017年; 6:1217–1226

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