Kadivar Mehdi, Khatami Shohreh, Mortazavi Yousef, Shokrgozar Mohammad Ali, Taghikhani Mohammad, Soleimani Masoud
Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
Biochem Biophys Res Commun. 2006 Feb 10;340(2):639-47. doi: 10.1016/j.bbrc.2005.12.047. Epub 2005 Dec 19.
Cardiomyocyte loss in the ischemically injured human heart often leads to irreversible defects in cardiac function. Recently, cellular cardiomyoplasty with mesenchymal stem cells, which are multipotent cells with the ability to differentiate into specialized cells under appropriate stimuli, has emerged as a new approach for repairing damaged myocardium. In the present study, the potential of human umbilical cord-derived mesenchymal stem cells to differentiate into cells with characteristics of cardiomyocyte was investigated. Mesenchymal stem cells were isolated from endothelial/subendothelial layers of the human umbilical cords using a method similar to that of human umbilical vein endothelial cell isolation. Isolated cells were characterized by transdifferentiation ability to adipocytes and osteoblasts, and also with flow cytometry analysis. After treatment with 5-azacytidine, the human umbilical cord-derived mesenchymal stem cells were morphologically transformed into cardiomyocyte-like cells and expressed cardiac differentiation markers. During the differentiation, cells were monitored by a phase contrast microscope and their morphological changes were demonstrated. Immunostaining of the differentiated cells for sarcomeric myosin (MF20), desmin, cardiac troponin I, and sarcomeric alpha-actinin was positive. RT-PCR analysis showed that these differentiated cells express cardiac-specific genes. Transmission electron microscopy revealed a cardiomyocyte-like ultrastructure and typical sarcomers. These observations confirm that human umbilical cord-derived mesenchymal stem cells can be chemically transformed into cardiomyocytes and can be considered as a source of cells for cellular cardiomyoplasty.
在遭受缺血损伤的人类心脏中,心肌细胞的丧失常常导致心脏功能出现不可逆的缺陷。最近,利用间充质干细胞进行细胞心肌成形术已成为修复受损心肌的一种新方法,间充质干细胞是一种多能细胞,在适当刺激下能够分化为特化细胞。在本研究中,对人脐带间充质干细胞分化为具有心肌细胞特征的细胞的潜力进行了研究。使用类似于人脐静脉内皮细胞分离的方法,从人脐带的内皮/内皮下层分离间充质干细胞。通过向脂肪细胞和成骨细胞的转分化能力以及流式细胞术分析对分离出的细胞进行表征。在用5-氮杂胞苷处理后,人脐带间充质干细胞在形态上转变为心肌样细胞并表达心脏分化标志物。在分化过程中,通过相差显微镜对细胞进行监测,并展示其形态变化。对分化细胞进行肌节肌球蛋白(MF20)、结蛋白、心肌肌钙蛋白I和肌节α-肌动蛋白的免疫染色呈阳性。逆转录聚合酶链反应分析表明,这些分化细胞表达心脏特异性基因。透射电子显微镜显示出心肌样超微结构和典型的肌节。这些观察结果证实,人脐带间充质干细胞可以通过化学方法转化为心肌细胞,并可被视为细胞心肌成形术的细胞来源。