Human bone marrow mesenchymal stem cells support the derivation and propagation of human induced pluripotent stem cells in culture.
Human bone marrow mesenchymal stem cells support the derivation and propagation of human induced pluripotent stem cells in culture.
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DOI：
10.1089/cell.2012.0064
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发表时间：
2013-05
影响因子：
1.6
通讯作者：
Li-fei Zhang;Wei-yan Zheng;Yebo Wang;Yingjia Wang;He Huang
中科院分区：
文献类型：
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作者：
Li-fei Zhang;Wei-yan Zheng;Yebo Wang;Yingjia Wang;He Huang
人类诱导多能干细胞（hiPSC）需要在临床适用的培养条件下生成和扩增，然后才能用于临床应用。在这项研究中，我们证明了来自不同供体的灭活的人间充质干细胞（hMSCs）可以用作饲养细胞，以支持hiPSC的建立和维持。我们在hMSC上产生和扩增的hiPSC表现出人胚胎干细胞（hESC）的典型形态，表达未分化的多能细胞标志物和基因，通过胚状体和畸胎瘤形成分化为所有三个胚层，并且在14代后保留正常的染色体核型。然而，我们发现hMSCs上hiPSCs的生成率为7.26%±2.09%，与小鼠胚胎成纤维细胞（MEFs）相比，hiPSCs在hMSCs上的扩增效率低于MEFs。来自不同供体和不同代次的hMSCs对结果没有影响。这些发现表明，hMSC可以用作饲养细胞以衍生和维持hiPSC，从而提供另一种用于产生和扩增hiPSC的临床可行的方法。然而，该系统中的细胞因子和粘附分子应被鉴定，以开发更好的hiPSCs临床培养条件。
Human induced pluripotent stem cells (hiPSCs) need to be generated and expanded under clinically applicable culture conditions before they can be used for clinical application. In this study, we demonstrate that inactivated human mesenchymal stem cells (hMSCs) from different donors can be used as feeder cells to support the establishment and maintenance of hiPSCs. The hiPSCs we generated and expanded on hMSCs exhibited the typical morphology of human embryonic stem cells (hESCs), expressed undifferentiated pluripotent cell markers and genes, differentiated into all three germ layers via embryoid body and teratoma formation, and retained a normal chromosomal karyotype after 14 passages. However, we found that the rate of hiPSCs generation on hMSCs was 7.26%±2.09% compared with that on mouse embryonic fibroblasts (MEFs), and the calculated expansion efficiency of hiPSCs on hMSCs was lower than that on MEFs. hMSCs from various donors and different passages did not influence the results. These findings suggest that hMSCs can be used as feeder cells to derive and maintain hiPSCs, and thus provide another clinically feasible method for generating and expanding hiPSCs. However, the cytokines and adhesion molecules in this system should be identified to develop a preferable clinical culture condition for hiPSCs.