Induced pluripotent stem (iPS) cells repair and regenerate infarcted myocardium.
Induced pluripotent stem (iPS) cells repair and regenerate infarcted myocardium.
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诱导多能干（iPS）细胞修复和再生梗塞心肌。
DOI：
10.1021/mp2001704
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发表时间：
2011-10-03
影响因子：
4.9
通讯作者：
Yan B
中科院分区：
文献类型：
--
作者：
Singla DK;Long X;Glass C;Singla RD;Yan B
迄今为止报道的心肌细胞分化来自小鼠和人成纤维细胞产生的iPS细胞。然而，没有关于从心室特异性细胞类型如H9c2细胞产生iPS细胞的文章。因此，最初从胚胎心室组织分离的转导的H9c2细胞是否能够产生iPS细胞并具有修复和再生梗死心肌的潜力仍然是完全难以捉摸的。我们用四种干细胞因子：Oct3/4、Sox2、Klf4和c-Myc转导H9c2细胞，并成功地将它们重编程为iPS细胞。这些iPS细胞能够分化为搏动的心肌细胞，并对心肌特异性肌节α-肌动蛋白和肌球蛋白重链蛋白进行阳性染色。移植到梗死心肌后2周，有新分化的心肌细胞和缝隙连接蛋白的形成，表明新形成的心肌细胞整合到天然心肌中。与MI组和MI + H9c2细胞组相比，iPS细胞移植组显著抑制心肌细胞凋亡和纤维化，改善心功能（p <0.05）。此外，在本研究中，我们的iPS细胞衍生的心肌细胞在体外和体内的分化与胚胎干细胞相当。总之，我们首次报道了H9c2细胞衍生的iPS细胞，其含有在细胞培养系统中分化为心肌细胞的潜力，并在体内修复和再生梗死心肌，改善心脏功能。
Cardiac myocyte differentiation reported thus far is from iPS cells generated from mouse and human fibroblasts. However, there is no article on the generation of iPS cells from cardiac ventricular specific cell types such as H9c2 cells. Therefore, whether transduced H9c2 cells, originally isolated from embryonic cardiac ventricular tissue, will be able to generate iPS cells and have the potential to repair and regenerate infarcted myocardium, remains completely elusive. We transduced H9c2 cells with four stemness factors; Oct3/4, Sox2, Klf4, and c-Myc, and successfully reprogrammed them into iPS cells. These iPS cells were able to differentiate into beating cardiac myocytes and positively stained for cardiac specific sarcomeric α-actin and myosin heavy chain proteins. Following transplantation in the infarcted myocardium, there were newly differentiated cardiac myocytes and formation of gap junction proteins at 2 weeks post-MI, suggesting newly formed cardiac myocytes were integrated into the native myocardium. Furthermore, transplanted iPS cells significantly (p<0.05) inhibited apoptosis and fibrosis and improved cardiac function compared with MI and MI+H9c2 cell groups. Moreover, our iPS cell derived cardiac myocyte differentiation in vitro and in vivo was comparable to embryonic stem cells in the present study. In conclusions we report for the first time that we have H9c2 cell-derived iPS cells which contain the potential to differentiate into cardiac myocytes in the cell culture system and repair and regenerate infarcted myocardium with improved cardiac function in vivo.
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影响因子：
20.1
作者：
Zhang J;Wilson GF;Soerens AG;Koonce CH;Yu J;Palecek SP;Thomson JA;Kamp TJ
通讯作者：
Kamp TJ
影响因子：
20.1
作者：
Kajstura, J;Rota, M;Anversa, P
通讯作者：
Anversa, P
影响因子：
4.8
作者：
Nussbaum, Jeannette;Minami, Elina;Murry, Charles E.
通讯作者：
Murry, Charles E.
DOI：
10.1152/ajpheart.00431.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Singla, Dinender K.;McDonald, Debbie E.
通讯作者：
McDonald, Debbie E.
影响因子：
6.6
作者：
Singla DK
通讯作者：
Singla DK