Barberi Tiziano, Bradbury Michelle, Dincer Zehra, Panagiotakos Georgia, Socci Nicholas D, Studer Lorenz
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, New York 10021, USA.
Nat Med. 2007 May;13(5):642-8. doi: 10.1038/nm1533. Epub 2007 Apr 8.
Human embryonic stem cells (hESCs) are a promising source for cell therapy in degenerative diseases. A key step in establishing the medical potential of hESCs is the development of techniques for the conversion of hESCs into tissue-restricted precursors suitable for transplantation. We recently described the derivation of multipotent mesenchymal precursors from hESCs. Nevertheless, our previous study was limited by the requirement for mouse feeders and the lack of in vivo data. Here we report a stroma-free induction system for deriving mesenchymal precursors. Selective culture conditions and fluorescence-activated cell sorting (FACS)-mediated purification yielded multipotent mesenchymal precursors and skeletal myoblasts. Skeletal muscle cells undergo in vitro maturation resulting in myotube formation and spontaneous twitching. We found that hESC-derived skeletal myoblasts were viable after transplantation into the tibialis anterior muscle of SCID/Beige mice, as assessed by bioluminescence imaging. Lack of teratoma formation and evidence of long-term myoblast engraftment suggests considerable potential for future therapeutic applications.
人胚胎干细胞(hESCs)是退行性疾病细胞治疗的一个有前景的细胞来源。确立hESCs医学潜力的关键一步是开发将hESCs转化为适合移植的组织特异性前体细胞的技术。我们最近描述了从hESCs中获得多能间充质前体细胞的方法。然而,我们之前的研究受到对小鼠饲养层的需求以及缺乏体内数据的限制。在此,我们报告一种用于获得间充质前体细胞的无基质诱导系统。选择性培养条件和荧光激活细胞分选(FACS)介导的纯化产生了多能间充质前体细胞和成肌细胞。骨骼肌细胞在体外成熟,导致肌管形成和自发抽搐。我们发现,通过生物发光成像评估,hESC来源的成肌细胞移植到SCID/米色小鼠的胫前肌后是存活的。未形成畸胎瘤以及长期成肌细胞植入的证据表明其在未来治疗应用中有相当大的潜力。