Directed differentiation of aged human bone marrow multipotent stem cells effectively generates dopamine neurons

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.