Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells

Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells
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DOI:
10.1096/fj.08-123661
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发表时间:
2009-06-01
期刊:
影响因子:
4.8
通讯作者:
Nakahata, Tatsutoshi
Nakahata, Tatsutoshi
中科院分区:
生物学2区
文献类型:
--
作者:
Chang, Hsi;Yoshimoto, Momoko;Nakahata, Tatsutoshi

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卫星细胞是负责骨骼肌出生后再生的肌源性干细胞。在这里,我们报告成功地在体外诱导Pax 7阳性卫星样细胞从小鼠胚胎干细胞(mES)。从mES细胞产生拟胚体,并在Matrigel包被的培养皿上用含有胎牛血清和马血清的Dulbecco改良Eagle培养基培养。Pax 7阳性卫星样细胞富集荧光激活细胞分选使用一种新的抗卫星细胞抗体,SM/C-2.6。SM/C-2.6阳性细胞在体外和体内均有效分化为骨骼肌纤维。此外,这些细胞表现出卫星细胞的特征,如在随后的肌肉损伤模型中广泛的自我更新能力,长达24周的长期植入,以及与成肌细胞移植相比具有显着高的植入效率的二次移植能力。这是第一份来自mES细胞的可移植的功能性卫星样细胞的报告,将为退行性肌肉疾病的新疗法提供基础。Chang,H.,Yoshimoto,M.,Umeda,K.,Iwasa,T.,水野,Y.,S.C.,山本,H.,Motohashi,N.,Yuko-Miyagoe-Suzuki,Takeda,S.,Heike,T.,Nakahata,T.从小鼠胚胎干细胞中产生可移植的功能性卫星样细胞。FASEB J. 23,1907-1919(2009)
Satellite cells are myogenic stem cells responsible for the postnatal regeneration of skeletal muscle. Here we report the successful in vitro induction of Pax7-positive satellite-like cells from mouse embryonic stem (mES) cells. Embryoid bodies were generated from mES cells and cultured on Matrigel-coated dishes with Dulbecco's modified Eagle medium containing fetal bovine serum and horse serum. Pax7-positive satellite-like cells were enriched by fluorescence-activated cell sorting using a novel anti-satellite cell antibody, SM/C-2.6. SM/C-2.6-positive cells efficiently differentiate into skeletal muscle fibers both in vitro and in vivo. Furthermore, the cells demonstrate satellite cell characteristics such as extensive self-renewal capacity in subsequent muscle injury model, long-term engraftment up to 24 wk, and the ability to be secondarily transplanted with remarkably high engraftment efficiency compared to myoblast transplantation. This is the first report of transplantable, functional satellite-like cells derived from mES cells and will provide a foundation for new therapies for degenerative muscle disorders.-Chang, H., Yoshimoto, M., Umeda, K., Iwasa, T., Mizuno, Y., Fukada, S., Yamamoto, H., Motohashi, N., Yuko-Miyagoe-Suzuki, Takeda, S., Heike, T., Nakahata, T. Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells. FASEB J. 23, 1907-1919 (2009)