Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells
Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells
复制标题
DOI：
10.1096/fj.09-145177
复制
发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Pillekamp, Frank
中科院分区：
文献类型：
--
作者：
Xi, Jiaoya;Khalil, Markus;Pillekamp, Frank
由胚胎干细胞(ESCs)和诱导多能干细胞(IPS)产生的心肌细胞被建议用于损伤心肌的再生。由于收缩特性对功能再生至关重要，我们比较了从ES细胞分化的心肌细胞(ESC-CMS)和iPS细胞(iPS-CMS)。以自体心肌作为对照。小鼠ESCs或iPS细胞在体外分化11d，与不可逆损伤的心肌组织切片共培养5~7d。年龄相近的活体胚胎脑室组织切片作为对照。研究负荷收缩时的力频关系(FFR)、钙离子、镍离子、硝苯地平、兰尼定、β-肾上腺素能和M受体的调节作用。FFR对ESC-CMS和iPS-CMS均为阴性。FFR在胚胎组织中呈阳性反应，经兰诺定处理后转为阴性。各组心肌细胞的收缩力和松弛时间均随钙离子浓度的升高而增大，硝苯地平使其减小。Ni2+降低了作用力。异丙肾上腺素(1mU M)对胚胎组织的增强作用最为明显(207+/-31%，n=7；ESC-CMS：123+/-5%，n=4；iPS-CMS：120+/-4%，n=8)。EC50值相似。IPS-CMS和ESC-CMS的收缩特性相似，但与同龄的心室组织有显著差异。这些结果表明肌浆网未成熟以及iPS-CMS和ESC-CMS的β-肾上腺素能反应。-Xi，J.，Khalil，M.，Shishechian，N.，Hannes，T.，Pfannkuche，K.，Leung，H.，Fatima，A.，Haustein，M.，Suhr，F.，Bloch，W.，Reppel，M.，M.，Saric，T.，Wernig，M.，Jaenisch，R.，Brockmeier，K.，Hescheler，J.，Pillekamp，F.FASE B J.24,2739-2751(2010)。Www.fasebj.org
Cardiomyocytes generated from embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells are suggested for repopulation of destroyed myocardium. Because contractile properties are crucial for functional regeneration, we compared cardiomyocytes differentiated from ES cells (ESC-CMs) and iPS cells (iPS-CMs). Native myocardium served as control. Murine ESCs or iPS cells were differentiated 11 d in vitro and cocultured 5-7 d with irreversibly injured myocardial tissue slices. Vital embryonic ventricular tissue slices of similar age served for comparison. Force-frequency relationship (FFR), effects of Ca2+, Ni2+, nifedipine, ryanodine, beta-adrenergic, and muscarinic modulation were studied during loaded contractions. FFR was negative for ESC-CMs and iPS-CMs. FFR was positive for embryonic tissue and turned negative after treatment with ryanodine. In all groups, force of contraction and relaxation time increased with the concentration of Ca2+ and decreased with nifedipine. Force was reduced by Ni2+. Isoproterenol (1 mu M) increased the force most pronounced in embryonic tissue (207 +/- 31%, n=7; ESC-CMs: 123 +/- 5%, n=4; iPS-CMs: 120 +/- 4%, n=8). EC50 values were similar. Contractile properties of iPS-CMs and ESC-CMs were similar, but they were significantly different from ventricular tissue of comparable age. The results indicate immaturity of the sarcoplasmic reticulum and the beta-adrenergic response of iPS-CMs and ESC-CMs.-Xi, J., Khalil, M., Shishechian, N., Hannes, T., Pfannkuche, K., Liang, H., Fatima, A., Haustein, M., Suhr, F., Bloch, W., Reppel, M., Saric, T., Wernig, M., Jaenisch, R., Brockmeier, K., Hescheler, J., Pillekamp, F. Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells. FASEB J. 24, 2739-2751 (2010). www.fasebj.org