Lin Lin, Bolund Lars, Luo Yonglun
Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, DK-8000, Aarhus C, Denmark.
Curr Stem Cell Res Ther. 2016;11(2):122-30. doi: 10.2174/1574888x10666150723150236.
Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing the importance of choosing the right sources of iPSCs, iPSC reprogramming methods, iPSC culture systems, embryoid body intermediates, pathway inhibitors, basal medium, serum, growth factors and culture surface coating. We also highlight some progress in the application of iPSC-MSCs in direct cell therapy, tissue engineering and gene therapy.
间充质干细胞(MSCs)是具有自我更新和多向分化能力的成体干细胞,可从多种成人组织中分离得到。然而,通过侵入性操作从成人组织中分离间充质干细胞用于细胞治疗受到阻碍,因为细胞稀少,且在体外培养和扩增时其增殖能力会减弱。源自诱导多能干细胞的人间充质干细胞(iPSC-MSCs)现已成为一种有前景的间充质干细胞替代细胞来源和再生医学细胞来源。包括我们团队在内的多个研究小组已报道成功诱导出功能性iPSC-MSCs,并将这些细胞应用于基于间充质干细胞的治疗测试。尽管如此,目前对于iPSC-MSCs在生产方法、安全性和有效性方面的经验和了解仍很有限。在本综述中,我们重点介绍了iPSC-MSCs研究中的方法学进展,阐述了选择合适的诱导多能干细胞来源、iPSC重编程方法、iPSC培养系统、胚状体中间体、信号通路抑制剂、基础培养基、血清、生长因子和培养表面包被的重要性。我们还重点介绍了iPSC-MSCs在直接细胞治疗、组织工程和基因治疗应用方面取得的一些进展。