Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling.
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DOI:
10.4103/1673-5374.193244
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发表时间:
2016-10
影响因子:
6.1
通讯作者:
Zhang C
Zhang C
中科院分区:
医学2区
文献类型:
--
作者:
Cao JQ;Liang YY;Li YQ;Zhang HL;Zhu YL;Geng J;Yang LQ;Feng SW;Yang J;Kong J;Zhang C

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脂肪干细胞已被证明可以通过旁分泌神经营养因子来促进周围神经再生。然而,尚不清楚这些细胞是否可以促进肌营养不良症的肌源性分化。将脂肪干细胞 (6 × 106) 注射到 mdx 小鼠腓肠肌的不同部位。在肌纤维中发现肌营养不良蛋白表达。 Akt、哺乳动物雷帕霉素靶蛋白 (mTOR)、eIF-4E 结合蛋白 1 和 S6 激酶 1 的磷酸化水平增加,并且 Akt/mTOR 通路被激活。同时,肌细胞生成素水平升高,而裂解的半胱天冬酶 3 和波形蛋白水平降低。肌纤维的坏死和纤维化减少。这些发现表明,脂肪干细胞通过抑制细胞凋亡和纤维化来促进肌肉细胞的再生和存活,从而减轻肌营养不良症中的肌肉损伤。
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 differentiation 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 fibers. 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 fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.