Volume 25, No 6, Jun 2015

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 25 Issue 6, June 2015: 655-673   |  Open Access

ORIGINAL ARTICLES

Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion

Xin Fu^1,*, Jun Xiao^2,*, Yuning Wei³, Sheng Li¹, Yan Liu¹, Jie Yin¹, Kun Sun⁴, Hao Sun⁴, Huating Wang⁵, Zongkang Zhang⁶, Bao-Ting Zhang⁶, Chun Sheng⁷, Hongyan Wang² and Ping Hu¹

¹State 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
²Key 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
³CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yueyang Road, Shanghai 200031, China
⁴Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
⁵Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
⁶School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
⁷Shanghai Normal University, Guilin Road, Shanghai 200234, China Correspondence: Ping Hu ; Hongyan Wang(hup@sibcb.ac.cn ; hongyanwang@sibcb.ac.cn)

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.

10.1038/cr.2015.58

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