Directed differentiation of aged human bone marrow multipotent stem cells effectively generates dopamine neurons
Directed differentiation of aged human bone marrow multipotent stem cells effectively generates dopamine neurons
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DOI：
10.1007/s11626-013-9701-6
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发表时间：
2014-04-01
影响因子：
2.1
通讯作者：
Liu, Houqi
中科院分区：
文献类型：
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作者：
Fan, Lixing;Hu, Kaimeng;Liu, Houqi
本研究旨在分离具有多向分化潜力的衰老人骨髓多能干细胞（hAMSCs），并直接诱导细胞产生多巴胺神经元，可用于帕金森病的治疗。我们比较了衰老人骨髓干细胞的不同培养方法，并鉴定出可以在体外增殖至少 60 倍的 hAMSC。使用RT-PCR和IHC，我们发现这些hAMSC表达多能基因，例如Oct4、Sox2和Nanog。体外研究还证明hAMSCs可以分化成三种胚层来源的细胞类型，例如成骨细胞、软骨形成细胞、脂肪形成细胞和肝细胞样细胞。 hAMSCs采用视黄酸、碱性成纤维细胞生长因子、Sonic Hedgehog两步法体外诱导20余天并撤血清后，可分化为多巴胺神经元，阳性率达70%，具有去极化分泌DA功能。总之，我们建议 hAMSCs 可作为细胞来源来开发药物治疗方法，以预防帕金森病的进展，特别是在老年人中。
This study aimed to isolate aged human bone marrow multipotent stem cells (hAMSCs) with the potential for multilineage differentiation and to directly induce the cells to generate dopamine neurons, which could be used for Parkinson's disease therapy. We compared different culture methods for stem cells from aged human bone marrow and identified hAMSCs that could proliferate in vitro for at least 60 doubling times. Using RT-PCR and IHC, we found that these hAMSCs expressed pluripotent genes, such as Oct4, Sox2, and Nanog. In vitro studies also proved that hAMSCs could differentiate into three germ layer-derived cell types, such as osteogenic, chondrogenic, adipogenic, and hepatocyte-liked cells. After induction for more than 20 d in vitro with retinoic acid, basic fibroblast growth factor, and sonic hedgehog using a two-step method and withdrawal of serum, hAMSCs could differentiate into dopamine neurons at the positive ratio of 70%, which showed DA secretion function upon depolarization. In conclusion, we suggest that hAMSCs can be used as cell sources to develop medical treatments to prevent the progression of Parkinson's disease, especially in aged persons.