非激活肌卫星细胞的体外扩增及其在肌肉衰老防治中的可能性应用

The reduction of muscle satellite cells is closely associated with muscle aging. How to obtain enough amount of quiescent satellite cells (QSC) for transplantation is a key for the therapy of muscle wasting and muscle diseases. Currently, the QSC may be isolated from fresh muscle tissues, but there is no proper expansion method available in vitro. We developed a novel method that could amplify the non-active satellite cell (NA-SC) as evidenced by pure Pax7+/MyoD- cells. Such NA-SCs have similar stemness, and ability to implant to SC niche. We propose that the resultant NA-SC cells may be used as QSC for muscle regeneration. To address this proposal, we plan to use series of animal models, and apply cell transplantation and physiological- biochemical analysis to optimize the expanding condition of NA-SC, investigate the mechanistic maintenance of stemness and implantation regulation. Simultaneously, we will explore the therapeutic possibility of the NA-SC in muscle aging and DMD disease.

肌卫星细胞的数量减少与肌肉衰老密切相关，如何有效获得大量的静态肌卫星细胞（Quiescent Satellite Cells, QSC）是防治肌肉衰老及其疾病的关键。目前只能从新鲜组织中直接分离获得少量的QSC，还没有理想的扩增方法。我们建立了一种新的培养方法，可大量扩增高纯度的Pax7+/MyoD-非激活性肌卫星细胞（NA-SC），且其干性特征、定植能力与QSC相同。 我们提出：由此扩增的NA-SC可替代QSC促进肌肉再生。为此，本课题将在此基础上通过系列动物模型、细胞移植实验和生理生化实验，系统地研究优化NA-SC的扩增条件，探讨其干性维持和定植的调控规律和分子机制；同时研究探讨NA-SC在肌肉衰老治疗和肌肉遗传病（DMD）的应用可能性，为其临床应用打下基础。

肌卫星细胞的数量减少与肌肉衰老密切相关，如何有效获得大量的静态肌卫星细胞（Quiescent Satellite Cells, QSC）是防治肌肉衰老及其疾病的关键。本课题通过系列动物模型、细胞移植实验和生理生化实验，系统地研究优化NA-SC的扩增条件，探讨其细胞干性维持和定植的调控规律和分子机制，得出：胸腺细胞培养上清TCM培养基能够大量扩增NA-SC，其有效成分可能是外泌体包裹的代谢酶类等。再者NA-SC干性特征以及定植能力等同QSC，可替代QSC促进肌肉再生。本课题的研究中，通过我们的特定培养条件扩出的NA-SC在肌肉衰老和损伤治疗中具有非常好的临床应用价值，同时也证实胸腺对肌肉再生的重要作用。

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