'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells
'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells
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DOI：
10.1016/j.yexcr.2007.04.028
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发表时间：
2007-07-15
影响因子：
3.7
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
--
作者：
Okamoto, Kazuma;Miyoshi, Shunichiro;Umezawa, Akihiro
细胞移植治疗严重心力衰竭是改善心功能受损的一种有前景的策略。近年来，骨髓细胞、内皮祖细胞、间充质干细胞、心脏干细胞和胚胎干细胞等一系列细胞类型已成为心脏修复的重要候选细胞来源。在目前的研究中，我们专注于胎盘作为细胞来源。人胎盘胎儿部分的绒毛板细胞是在分娩后通过原代培养法获得的，并且在本研究中产生的细胞具有Y性染色体，表明这些细胞来自胎儿。这些细胞可能表达“工作”心肌细胞特异性基因，如心肌肌球蛋白重链7[1]、心房肌球蛋白轻链、通过基因芯片分析的心肌α-肌动蛋白，以及通过RT-PCR分析的Csx/Nkx 2.5、GATA 4，通过免疫组织化学分析的心肌肌钙蛋白-I和连接蛋白43。这些细胞能够分化为心肌细胞。心肌肌钙蛋白-I和连接蛋白43在心肌分化后的细胞间接触部位显示出不连续的定位模式，表明绒毛膜中胚层含有大量具有心肌分化潜能的细胞。在与鼠胎儿心肌细胞共培养后3天，细胞开始自发搏动，并且搏动细胞的频率在第10天达到最大值。心肌细胞的收缩是有节律的和同步的，表明细胞之间存在电通信。胎盘来源的人胎儿细胞可能对无法提供骨髓细胞但希望接受基于干细胞的心脏治疗的患者有用。(C)2007爱思唯尔公司All rights reserved.
The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, includingbone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiornyocyte-specific genes such as cardiac myosin heavy chain 7[1, atrial myosin light chain, cardiac a-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiornyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiornyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy. (C) 2007 Elsevier Inc. All rights reserved.