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

Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion.
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炎症相关细胞因子的组合可促进肌肉干细胞的长期扩增。

DOI:
10.1038/cr.2015.58
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发表时间:
2015-06
期刊:
影响因子:
44.1
通讯作者:
--
中科院分区:
生物学1区
文献类型:
--
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肌肉干细胞(MuSCs,卫星细胞)是肌肉再生的主要贡献者。像大多数成体干细胞一样,musc在体外的长期扩增是困难的。在体外培养后,MuSCs的体内肌肉再生能力很快丧失,这阻碍了MuSCs在细胞治疗中的潜在应用。在这里,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,由T细胞分泌的四种促炎细胞因子IL-1α、IL-13、TNF-α和IFN-γ的结合能够刺激MuSC在体内损伤后的增殖,并促进MuSC在体外的连续扩增。扩增后的musc可以补充内源性干细胞库,并且能够在单次移植后在体内修复多轮肌肉损伤。体外系统的建立为我们扩展功能性musc修复肌肉损伤提供了一种有力的方法。
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.
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