急性心肌梗死后人诱导多能干细胞衍生心肌细胞与人间充质干细胞的比较。
Comparison of human induced pluripotent stem-cell derived cardiomyocytes with human mesenchymal stem cells following acute myocardial infarction.
作者信息
Citro Lucas, Naidu Shan, Hassan Fatemat, Kuppusamy M Lakshmi, Kuppusamy Periannan, Angelos Mark G, Khan Mahmood
机构信息
Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, 43210, United States of America; Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, 43210, United States of America.
Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth College, New Hampshire, 03766, United States of America.
出版信息
PLoS One. 2014 Dec 31;9(12):e116281. doi: 10.1371/journal.pone.0116281. eCollection 2014.
INTRODUCTION
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have recently been shown to express key cardiac proteins and improve in vivo cardiac function when administered following myocardial infarction. However, the efficacy of hiPSC-derived cell therapies, in direct comparison to current, well-established stem cell-based therapies, is yet to be elucidated. The goal of the current study was to compare the therapeutic efficacy of human mesenchymal stem cells (hMSCs) with hiPSC-CMs in mitigating myocardial infarction (MI).
METHODS
Male athymic nude hyrats were subjected to permanent ligation of the left-anterior-descending (LAD) coronary artery to induce acute MI. Four experimental groups were studied: 1) control (non-MI), 2) MI, 3) hMSCs (MI+MSC), and 4) hiPSC-CMs (MI+hiPSC-derived cardiomyocytes). The hiPSC-CMs and hMSCs were labeled with superparamagnetic iron oxide (SPIO) in vitro to track the transplanted cells in the ischemic heart by high-field cardiac MRI. These cells were injected into the ischemic heart 30-min after LAD ligation. Four-weeks after MI, cardiac MRI was performed to track the transplanted cells in the infarct heart. Additionally, echocardiography (M-mode) was performed to evaluate the cardiac function. Immunohistological and western blot studies were performed to assess the cell tracking, engraftment and cardiac fibrosis in the infarct heart tissues.
RESULTS
Echocardiography data showed a significantly improved cardiac function in the hiPSC-CMs and hMSCs groups, when compared to MI. Immunohistological studies showed expression of connexin-43, α-actinin and myosin heavy chain in engrafted hiPSC-CMs. Cardiac fibrosis was significantly decreased in hiPSC-CMs group when compared to hMSCs or MI groups. Overall, this study demonstrated improved cardiac function with decreased fibrosis with both hiPSC-CMs and hMSCs groups when compared with MI group.
引言
最近研究表明，人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）可表达关键心脏蛋白，并在心肌梗死后给药时改善体内心脏功能。然而，与目前成熟的基于干细胞的疗法直接比较，hiPSC衍生细胞疗法的疗效尚待阐明。本研究的目的是比较人间充质干细胞（hMSCs）与hiPSC-CMs在减轻心肌梗死（MI）方面的治疗效果。
方法
雄性无胸腺裸大鼠接受左前降支（LAD）冠状动脉永久性结扎以诱导急性心肌梗死。研究了四个实验组：1）对照组（非心肌梗死），2）心肌梗死组，3）hMSCs组（心肌梗死+间充质干细胞），4）hiPSC-CMs组（心肌梗死+hiPSC衍生的心肌细胞）。hiPSC-CMs和hMSCs在体外用超顺磁性氧化铁（SPIO）标记，以便通过高场心脏MRI追踪缺血心脏中的移植细胞。这些细胞在LAD结扎后30分钟注入缺血心脏。心肌梗死后四周，进行心脏MRI以追踪梗死心脏中的移植细胞。此外，进行超声心动图（M型）以评估心脏功能。进行免疫组织学和蛋白质印迹研究以评估梗死心脏组织中的细胞追踪、植入和心脏纤维化。
结果
超声心动图数据显示，与心肌梗死组相比，hiPSC-CMs组和hMSCs组的心脏功能有显著改善。免疫组织学研究显示，植入的hiPSC-CMs中连接蛋白-43、α-辅肌动蛋白和肌球蛋白重链的表达。与hMSCs组或心肌梗死组相比，hiPSC-CMs组的心脏纤维化显著降低。总体而言，本研究表明，与心肌梗死组相比，hiPSC-CMs组和hMSCs组的心脏功能均有改善，纤维化程度降低。
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