Fu Xin, Xiao Jun, Wei Yuning, Li Sheng, Liu Yan, Yin Jie, Sun Kun, Sun Hao, Wang Huating, Zhang Zongkang, Zhang Bao-Ting, Sheng Chun, Wang Hongyan, Hu Ping
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cell Res. 2015 Jun;25(6):655-73. doi: 10.1038/cr.2015.58. Epub 2015 May 15.
Muscle stem cells (MuSCs, satellite cells) are the major contributor to muscle regeneration. Like most adult stem cells, long-term expansion of MuSCs in vitro is difficult. The in vivo muscle regeneration abilities of MuSCs are quickly lost after culturing in vitro, which prevents the potential applications of MuSCs in cell-based therapies. Here, we establish a system to serially expand MuSCs in vitro for over 20 passages by mimicking the endogenous microenvironment. We identified that the combination of four pro-inflammatory cytokines, IL-1α, IL-13, TNF-α, and IFN-γ, secreted by T cells was able to stimulate MuSC proliferation in vivo upon injury and promote serial expansion of MuSCs in vitro. The expanded MuSCs can replenish the endogenous stem cell pool and are capable of repairing multiple rounds of muscle injuries in vivo after a single transplantation. The establishment of the in vitro system provides us a powerful method to expand functional MuSCs to repair muscle injuries.
肌肉干细胞（MuSCs，卫星细胞）是肌肉再生的主要贡献者。与大多数成体干细胞一样，在体外长期扩增MuSCs很困难。MuSCs的体内肌肉再生能力在体外培养后会迅速丧失，这阻碍了MuSCs在基于细胞的治疗中的潜在应用。在此，我们建立了一个系统，通过模拟内源性微环境在体外连续扩增MuSCs超过20代。我们发现，T细胞分泌的四种促炎细胞因子IL-1α、IL-13、TNF-α和IFN-γ的组合能够在损伤后刺激体内MuSC增殖，并促进体外MuSCs的连续扩增。扩增后的MuSCs可以补充内源性干细胞池，并且在单次移植后能够在体内修复多轮肌肉损伤。体外系统的建立为我们提供了一种强大的方法来扩增功能性MuSCs以修复肌肉损伤。
