Wei Heming, Tan Grace, Qiu Suhua, Kong Geraldine, Yong Pearly, Koh Caihong, Ooi Ting Huay, Lim Sze Yun, Wong Philip, Gan Shu Uin, Shim Winston
Research and Development Unit, National Heart Centre Singapore, Singapore.
Stem Cell Res. 2012 Sep;9(2):87-100. doi: 10.1016/j.scr.2012.04.003. Epub 2012 Apr 24.
Cardiomyocytes (CMs) and mesenchymal stem cells (MSCs) are important cell types for cardiac repair post myocardial infarction. Here we proved that both CMs and MSCs can be simultaneously generated from human induced pluripotent stem cells (hiPSCs) via a pro-mesoderm differentiation strategy. Two hiPSC lines, hiPSC (1) and hiPSC (2) were generated from human dermal fibroblasts using OCT-4, SOX-2, KLF-4, c-Myc via retroviral-based reprogramming. H9 human embryonic stem cells (hESCs) served as control. CMs and MSCs were co-generated from hiPSCs and hESCs via embryoid body-dependent cardiac differentiation protocol involving a serum-free and insulin-depleted medium containing a p38 MAPK inhibitor, SB 203580. Comparing to bone marrow and umbilical cord blood-derived MSCs, hiPSC-derived MSCs (iMSCs) expressed common MSC markers and were capable of adipogenesis, osteogenesis and chondrogenesis. Moreover, iMSCs continuously proliferated for more than 32 population doublings without cellular senescence and showed superior pro-angiogenic and wound healing properties. In summary, we generated a large number of homogenous MSCs in conjunction with CMs in a low-cost and efficient one step manner. Functionally competent CMs and MSCs co-generated from hiPSCs may be useful for autologous cardiac repair.
心肌细胞（CMs）和间充质干细胞（MSCs）是心肌梗死后心脏修复的重要细胞类型。在此，我们证明了通过促中胚层分化策略，CMs和MSCs均可从人诱导多能干细胞（hiPSCs）中同时生成。使用OCT-4、SOX-2、KLF-4、c-Myc通过基于逆转录病毒的重编程方法，从人皮肤成纤维细胞中生成了两条hiPSC系，即hiPSC(1)和hiPSC(2)。H9人胚胎干细胞（hESCs）用作对照。通过涉及不含血清和胰岛素且含有p38丝裂原活化蛋白激酶抑制剂SB 203580的培养基的胚胎体依赖性心脏分化方案，从hiPSCs和hESCs中共同生成CMs和MSCs。与骨髓和脐带血来源的MSCs相比，hiPSC来源的MSCs（iMSCs）表达常见的MSC标志物，并且能够进行脂肪生成、成骨和成软骨。此外，iMSCs连续增殖超过32个群体倍增而无细胞衰老，并且表现出卓越的促血管生成和伤口愈合特性。总之，我们以低成本、高效的一步方式同时生成了大量与CMs结合的同质MSCs。从hiPSCs共同生成的功能正常的CMs和MSCs可能对自体心脏修复有用。
