中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1638-1643.doi: 10.4103/1673-5374.193244

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

脂肪干细胞通过旁分泌改善肌营养不良的成肌分化

  

  • 收稿日期:2016-09-01 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    中国国家自然科学基金项目（30870851, 81271401）；中国国家自然科学基金与广东省自然科学基金联合项目（U1032004）

Adipose-derived stem cells enhance myogenic di?erentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

Ji-qing Cao1, 2, #, Ying-yin Liang1, 2, #, Ya-qin Li1, 2, Hui-li Zhang1, 2, Yu-ling Zhu3, Jia Geng4, Li-qing Yang1, Shan-wei Feng1, Juan Yang1, 2, Jie Kong1, 2, Cheng Zhang1, *   

  1. 1 Department of Neurology, First Afliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China 2 Guangdong Key Laboratory for the Diagnosis and Treatment of Major Neurological Disease, First Afliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China 3 First Afliated Hospital, Kunming Medical College, Kunming, Yunnan Province, China 4 Department of Neurology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China
  • Received:2016-09-01 Online:2016-10-31 Published:2016-10-31
  • Contact: Cheng Zhang, Ph.D., chengzhang100@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 30370510, 30870851, 81271401; the Joint Fund of National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province of China, No. U1032004.

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摘要：

有研究发现脂肪干细胞可通过旁分泌营养因子促进周围神经再生，是否也可通过此途径参与肌营养不良后的成肌分化呢？实验对敲除抗肌萎缩蛋白基因的mdx小鼠腓肠肌多点注射6 × 106个SD大鼠的脂肪干细胞后，发现肌纤维中出现抗肌萎缩蛋白，且Akt，mTOR4E-BP1和S6的磷酸化水平增加，激活Akt/mTOR通路，同时肌细胞生成素水平升高，caspase 3和波形蛋白水平下降，且肌纤维中细胞坏死和纤维化减少。结果数据说明脂肪干细胞可通过抑制细胞凋亡和纤维化，促进肌细胞的再生和存活，改善肌肉营养不良。 

orcid: 0000-0002-9722-243X (Cheng Zhang)

关键词: 神经再生, Duchenne型肌营养不良症, 脂肪干细胞, 成肌分化, 旁分泌途径, 抗肌萎缩蛋白

Abstract: Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic di?erentiation in muscular dystrophy. Adipose-derived stem cells (6 × 106) were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fbers. Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), eIF-4E binding protein 1 and S6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fbrosis were reduced in the muscle fbers. Tese fndings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fbrosis, thereby alleviating muscle damage in muscular dystrophy.

Key words: nerve regeneration, Duchenne muscular dystrophy, adipose-derived stem cells, myogenic di?erentiation, paracrine pathway, dystrophin, neural regeneration