Colletti Evan J, Airey Judith A, Liu Wansheng, Simmons Paul J, Zanjani Esmail D, Porada Christopher D, Almeida-Porada Graça
Department of Animal Biotechnology, University of Nevada at Reno, Reno, NV 89557, USA.
Stem Cell Res. 2009 Mar;2(2):125-38. doi: 10.1016/j.scr.2008.08.002. Epub 2008 Sep 16.
Human mesenchymal stem cells (MSC) hold great promise for cellular replacement therapies. Despite their contributing to phenotypically distinct cells in multiple tissues, controversy remains regarding whether the phenotype switch results from a true differentiation process. Here, we studied the events occurring during the first 120 h after human MSC transplantation into a large animal model. We demonstrate that MSC, shortly after engrafting different tissues, undergo proliferation and rapidly initiate the differentiative process, changing their phenotype into tissue-specific cells. Thus, the final level of tissue-specific cell contribution is not determined solely by the initial level of engraftment of the MSC within that organ, but rather by the proliferative capability of the ensuing tissue-specific cells into which the MSC rapidly differentiate. Furthermore, we show that true differentiation, and not cell fusion or transfer of mitochondria or membrane-derived vesicles between transplanted and resident cells, is the primary mechanism contributing to the change of phenotype of MSC upon transplantation.
人间充质干细胞（MSC）在细胞替代疗法方面具有巨大潜力。尽管它们能在多种组织中分化为表型各异的细胞，但关于这种表型转换是否源于真正的分化过程仍存在争议。在此，我们研究了将人间充质干细胞移植到大型动物模型后最初120小时内发生的事件。我们证明，间充质干细胞在植入不同组织后不久便开始增殖，并迅速启动分化过程，将其表型转变为组织特异性细胞。因此，组织特异性细胞的最终贡献水平并非仅由该器官内间充质干细胞的初始植入水平决定，而是由间充质干细胞迅速分化而成的后续组织特异性细胞的增殖能力决定。此外，我们表明，真正的分化而非细胞融合、线粒体或膜衍生小泡在移植细胞与驻留细胞之间的转移，是移植时间充质干细胞表型改变的主要机制。
