人类多能干细胞(hPSC)衍生肌源性祖细胞(MPC)在移植后会发育为成熟的静止卫星细胞,这一成果由美国约翰霍普金斯大学医学院Gabsang Lee和Kathryn R. Wagner课题组合作取得。2022年4月7日出版的《细胞-干细胞》杂志发表了这项成果。
研究人员使用MPC特异性荧光报告系统(PAX7::GFP),发现hPSC衍生的MPC可以促进局部损伤和缺乏肌营养不良蛋白(mdx)小鼠的肌纤维再生。研究还发现PAX7::GFP MPC的一个亚群植入再生肌纤维的基底层内,并维持在静止状态,这有助于再损伤和mdx小鼠模型中肌纤维的再生。PAX7::GFP MPCs亚群经历了一个成熟过程,并重塑了它们的分子特征,使其在体内植入后类似于晚期胎儿MPCs/成人卫星细胞。这些体内成熟的PAX7::GFP MPC保留了细胞自主再生能力,并且可以在小鼠次级受体生态位中重新增殖,这为基于hPSC的肌肉疾病细胞治疗提供了理论依据。
据悉,hPSC衍生的肌源性祖细胞移植是一种治疗各种退行性肌肉疾病的潜在方法。
附:英文原文
Title: Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment
Author: Congshan Sun, Suraj Kannan, In Young Choi, HoTae Lim, Hao Zhang, Grace S. Chen, Nancy Zhang, Seong-Hyun Park, Carlo Serra, Shama R. Iyer, Thomas E. Lloyd, Chulan Kwon, Richard M. Lovering, Su Bin Lim, Peter Andersen, Kathryn R. Wagner, Gabsang Lee
Issue&Volume: 2022/04/07
Abstract: Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantationis a promising therapeutic approach for a variety of degenerative muscle disorders.Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstratethat hPSC-derived MPCs can contribute to the regeneration of myofibers in mice followinglocal injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal laminaof regenerated myofibers, adopt a quiescent state, and contribute to regenerationupon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process and remodeltheir molecular characteristics to resemble those of late-stage fetal MPCs/adult satellitecells following in vivo engraftment. These in-vivo-matured PAX7::GFP MPCs retain a cell-autonomous ability to regenerate and can repopulatein the niche of secondary recipient mice, providing a proof of principle for futurehPSC-based cell therapy for muscle disorders.
DOI: 10.1016/j.stem.2022.03.004
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00102-3
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
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