Department of Anatomy, Histology, and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
Stem Cells Dev. 2012 May 20;21(8):1367-79. doi: 10.1089/scd.2011.0280. Epub 2011 Oct 27.
Stem cell therapy is a promising therapeutic strategy for treating myocardial infarction (MI). However, it is necessary to identify ideal adult stem cells for transplantation and explore mechanisms of the transplanted cells in improving cardiac functions after MI. In this study, a population of embryonic-like stem cells (ELSCs) was isolated from rat bone marrow. The cells express pluripotent stem cell transcriptional factors and present high proliferative activity on mouse embryonic fibroblast feeder. ELSCs retain clonal expansion and may form embryoid-like bodies in soft agarose containing leukemia inhibitory factor and basic fibroblast growth factor. The cells of the embryoid-like bodies can differentiate into the cells from 3 germ layers. Under induction, the cells can differentiate into cardiomyocytes and endothelial cells. In MI models of female rats, the transplantation of preinduced ELSCs of male rats reduce scar area and improve cardiac function significantly. Comparing with marrow-derived mesenchymal stem cells and ELSCs without induction, effects of the preinduced ELSCs on myocardial repair and improvement of cardiac function are greater. Survival of the transplanted cells in the peri-infarcted and infarcted regions was examined by fluorescence in situ hybridization. Y chromosome-positive cells may differentiate toward cardiomyocytes and express cTnT and Cx43. Cx43 expression was observed at conjunction of Y chromosome-positive cells and recipient cardiomyocytes. Some Y chromosome-positive cells express CD31 and incorporate into the microvessels in the infarcted tissue. These results suggest that a population of ELSCs resides in rat bone marrow and display similar biological characteristics of ESCs. ELSCs can differentiate into cardiomyocytes and endothelial cells and contribute to cardiomyogenesis and angiogenesis in vivo. Cardiac function after MI may be significantly improved with transplantation of the preinduced ELSCs. Therefore, ELSCs are novel seed cells for stem cell transplantation in regenerative medicine.
干细胞治疗是一种很有前途的治疗心肌梗死（MI）的治疗策略。然而，有必要确定理想的成体干细胞进行移植，并探讨移植细胞改善 MI 后心脏功能的机制。在这项研究中，从大鼠骨髓中分离出了一群胚胎样干细胞（ELSCs）。这些细胞表达多能干细胞转录因子，并在小鼠胚胎成纤维细胞饲养层上表现出高增殖活性。ELSCs 保持克隆扩增，并在含有白血病抑制因子和碱性成纤维细胞生长因子的软琼脂中可能形成类胚体。类胚体的细胞可以分化为 3 个胚层的细胞。在诱导条件下，这些细胞可以分化为心肌细胞和内皮细胞。在雌性大鼠的 MI 模型中，雄性大鼠预诱导的 ELSCs 移植可显著减少疤痕面积并改善心脏功能。与骨髓来源的间充质干细胞和未经诱导的 ELSCs 相比，预诱导的 ELSCs 对心肌修复和心脏功能改善的作用更大。通过荧光原位杂交检查移植细胞在梗死周边和梗死区的存活情况。Y 染色体阳性细胞可能向心肌细胞分化，并表达 cTnT 和 Cx43。在 Y 染色体阳性细胞和受者心肌细胞的连接处观察到 Cx43 表达。一些 Y 染色体阳性细胞表达 CD31 并整合到梗死组织中的微血管中。这些结果表明，大鼠骨髓中存在一群 ELSCs，表现出与 ESC 相似的生物学特征。ELSCs 可分化为心肌细胞和内皮细胞，并有助于体内的心肌发生和血管生成。MI 后心脏功能可能通过移植预诱导的 ELSCs 得到显著改善。因此，ELSCs 是再生医学中干细胞移植的新型种子细胞。
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