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定向诱导人胚胎干细胞的体外肌生成及其体内移植。

Directed in vitro myogenesis of human embryonic stem cells and their in vivo engraftment.

机构信息

Department of Bioengineering, University of California San Diego, San Diego, California, United States of America.

出版信息

PLoS One. 2013 Aug 19;8(8):e72023. doi: 10.1371/journal.pone.0072023. eCollection 2013.

DOI:10.1371/journal.pone.0072023
PMID:23977197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3747108/
Abstract

Development of human embryonic stem cell (hESC)-based therapy requires derivation of in vitro expandable cell populations that can readily differentiate to specified cell types and engraft upon transplantation. Here, we report that hESCs can differentiate into skeletal muscle cells without genetic manipulation. This is achieved through the isolation of cells expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), following embryoid body (EB) formation. The ESC-derived cells differentiated into myoblasts in vitro as evident by upregulation of various myogenic genes, irrespective of the presence of serum in the medium. This result is further corroborated by the presence of sarcomeric myosin and desmin, markers for terminally differentiated cells. When transplanted in vivo, these pre-myogenically committed cells were viable in tibialis anterior muscles 14 days post-implantation. These hESC-derived cells, which readily undergo myogenic differentiation in culture medium containing serum, could be a viable cell source for skeletal muscle repair and tissue engineering to ameliorate various muscle wasting diseases.

摘要

基于人胚胎干细胞(hESC)的治疗方法的发展需要衍生出可在体外大量扩增的细胞群体,这些细胞能够轻易地分化为特定的细胞类型,并在移植后植入。在这里,我们报告说,hESC 可以在没有遗传操作的情况下分化为骨骼肌细胞。这是通过在胚胎体(EB)形成后分离表达中胚层标志物血小板衍生生长因子受体-α(PDGFRA)的细胞来实现的。ESC 衍生的细胞在体外分化为成肌细胞,这一点可通过各种肌生成基因的上调得到证实,而与培养基中是否存在血清无关。这一结果进一步得到了肌球蛋白和结蛋白(终末分化细胞的标志物)的存在的证实。当将这些细胞移植到体内时,它们在植入后 14 天仍存在于比目鱼肌中。这些 hESC 衍生的细胞在含有血清的培养基中很容易进行成肌分化,它们可能是骨骼肌修复和组织工程的可行细胞来源,以改善各种肌肉消耗性疾病。

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