Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells
Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells
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DOI：
10.1089/scd.2011.0435
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
Yang, Phillip C.
中科院分区：
文献类型：
--
作者：
Ge, Xiaohu;Wang, I-Ning E.;Yang, Phillip C.
人羊膜间充质干细胞（hAMSC）表现出部分多能性特征，具有Oct 4和Nanog基因的强表达和免疫调节特性，其特征在于不存在HLA-DR和存在HLA-G和CD 59。将hAMSC重编程为诱导多能干细胞（iPSC），其产生有希望的通用心脏细胞来源。hAMSC衍生的iPSC（MiPSC）成功地经历了稳健的心脏分化以产生心肌细胞。本研究调查了hAMSC和MiPSC的3个关键性质：（1）部分多能hAMSC产生MiPSC的重编程效率;（2）hAMSC和MiPSC的免疫调节性质;和（3）MiPSC的心脏分化潜力。在用含有4种Yamanaka因子的单一整合多顺反子载体转导hAMSC后10天内观察到特征性iPSC集落形成。免疫组织学和逆转录-聚合酶链反应分析显示，MiPSC表达干细胞表面标志物和多能特异性基因。此外，hAMSC和MiPSC表现出免疫调节特性，使得能够在SVJ小鼠中成功植入。最后，MiPSC的心脏分化表现出强大的自发收缩性，跨膜的特征性钙瞬变，心脏基因和成熟心脏表型的高表达，以及与心肌细胞相当的收缩力。我们的研究结果表明，hAMSC被高效率地重编程为MiPSC，其具有多能性、免疫调节性和心前特性。MiPSC衍生的心脏细胞表达c-kit细胞表面标志物，其可用于纯化心脏细胞群并实现同种异体心脏干细胞治疗。
Human amniotic mesenchymal stem cells (hAMSCs) demonstrated partially pluripotent characteristics with a strong expression of Oct4 and Nanog genes and immunomodulatory properties characterized by the absence of HLA-DR and the presence of HLA-G and CD59. The hAMSCs were reprogrammed into induced pluripotent stem cells (iPSCs) that generate a promising source of universal cardiac cells. The hAMSC-derived iPSCs (MiPSCs) successfully underwent robust cardiac differentiation to generate cardiomyocytes. This study investigated 3 key properties of the hAMSCs and MiPSCs: (1) the reprogramming efficiency of the partially pluripotent hAMSCs to generate MiPSCs; (2) immunomodulatory properties of the hAMSCs and MiPSCs; and (3) the cardiac differentiation potential of the MiPSCs. The characteristic iPSC colony formation was observed within 10 days after the transduction of the hAMSCs with a single integration polycistronic vector containing 4 Yamanaka factors. Immunohistology and reverse transcription-polymerase chain reaction assays revealed that the MiPSCs expressed stem cell surface markers and pluripotency-specific genes. Furthermore, the hAMSCs and MiPSCs demonstrated immunomodulatory properties enabling successful engraftment in the SVJ mice. Finally, the cardiac differentiation of MiPSCs exhibited robust spontaneous contractility, characteristic calcium transience across the membrane, a high expression of cardiac genes and mature cardiac phenotypes, and a contractile force comparable to cardiomyocytes. Our results demonstrated that the hAMSCs are reprogrammed with a high efficiency into MiPSCs, which possess pluripotent, immunomodulatory, and precardiac properties. The MiPSC-derived cardiac cells express a c-kit cell surface marker, which may be employed to purify the cardiac cell population and enable allogeneic cardiac stem cell therapy.