Generation of functional cardiomyocytes from mouse induced pluripotent stem cells

Generation of functional cardiomyocytes from mouse induced pluripotent stem cells
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DOI:
10.1016/j.ijcard.2010.08.052
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发表时间:
2011-12-15
影响因子:
3.5
通讯作者:
Park, Se Pill
Park, Se Pill
中科院分区:
医学2区
文献类型:
--
作者:
So, Kyoung Ha;Han, Young Joon;Park, Se Pill

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背景:诱导多能干细胞(iPS)允许衍生自体分化细胞用于细胞治疗。本研究旨在比较小鼠iPS细胞与胚胎干细胞(ES细胞)的心肌分化潜能,证明它们可以产生功能性的心肌细胞。方法:采用慢病毒介导的方法,从小鼠胚胎成纤维细胞中分离iPS细胞,并表达Oct 4/Sox 2/Klf 4/C-myc四种转录因子。为了诱导心肌细胞分化,使用双培养基培养方案诱导iPS-S-6或D3-ES细胞形成胚状体(EB),然后铺在明胶包被的平板上并维持在DMEM中。将感染EB的世代分为早期(d8-d11)、中期(d12-d15)和晚期(d16-20),iPS细胞在早期表现出与ES细胞相似的特性。在中期组的iPS细胞中,与ES细胞相比,收缩EB的比例显著增加,并且在晚期组的细胞中,差异持续存在(p
Background: Induced pluripotent stem (iPS) cells allow derivation of autologous differentiated cells for cell therapy. The purpose of this study was to compare the cardiac differentiation potential of mouse iPS cells with embryonic stem (ES) cells and demonstrate that they could produce functional cardiomyocytes.Methods: iPS cells were prepared from mouse embryonic fibroblasts by lentiviral mediated expression of four transcription factors (Oct4/Sox2/Klf4/C-myc). To induce cardiac cell differentiation, iPS-S-6 or D3-ES cells were induced to form embryoid bodies (EBs) using a two-medium culture protocol, then plated onto gelatin-coated plates and maintained in DMEM.Results: Following classification of the generation periods of contracting EBs into early (d8-d11), middle (d12-d15) and late (d16-20), iPS cells in the early period exhibited characteristics similar to ES cells. In iPS cells from the middle period group, the ratio of contracting EBs was significantly increased compared to ES cells, and the difference persisted in cells from the late period group (p