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脂肪干细胞应用对甘油诱导的肌肉损伤后终板再生的影响。

Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage.

作者信息

Rigon Matteo, Hörner Sarah Janice, Straka Tatjana, Bieback Karen, Gretz Norbert, Hafner Mathias, Rudolf Rüdiger

机构信息

Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, Mannheim, Germany.

Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

出版信息

Front Mol Neurosci. 2020 Jun 23;13:107. doi: 10.3389/fnmol.2020.00107. eCollection 2020.

Abstract

Amongst other approaches, adipose-derived stromal cells (ASCs) have recently been tested with respect to their regenerative capacity for treatment of neuromuscular disorders. While beneficial effects of ASCs on muscle recovery were observed previously, their impact on regeneration of neuromuscular junctions (NMJs) is unclear. Here, we used a murine glycerol damage model to study disruption and regeneration of NMJs and to evaluate the effects of systemic application of ASCs on muscle and NMJ recovery. In mice that were not treated with ASCs, a differential response of NMJ pre- and post-synapses to glycerol-induced damage was observed. While post-synapses were still present in regions that were necrotic and lacking actin and dystrophin, pre-synapses disappeared soon in those affected areas. Partial regeneration of NMJs occurred within 11 days after damage. ASC treatment slightly enhanced NMJ recovery and reduced the loss of presynaptic sites, but also led to a late phase of muscle necrosis and fibrosis. In summary, the results suggest a differential sensitivity of NMJ pre- and post-synapses to glycerol-induced muscle damage and that the use of ASC for the treatment of neuromuscular disorders needs further careful evaluation.

摘要

在其他方法中,脂肪来源的基质细胞(ASC)最近已就其治疗神经肌肉疾病的再生能力进行了测试。虽然之前观察到ASC对肌肉恢复有有益作用,但其对神经肌肉接头(NMJ)再生的影响尚不清楚。在这里,我们使用小鼠甘油损伤模型来研究NMJ的破坏和再生,并评估全身应用ASC对肌肉和NMJ恢复的影响。在未用ASC治疗的小鼠中,观察到NMJ突触前和突触后对甘油诱导损伤的不同反应。虽然突触后仍存在于坏死且缺乏肌动蛋白和抗肌萎缩蛋白的区域,但突触前在这些受影响区域很快消失。损伤后11天内NMJ发生部分再生。ASC治疗略微增强了NMJ恢复并减少了突触前位点的损失,但也导致了肌肉坏死和纤维化的后期阶段。总之,结果表明NMJ突触前和突触后对甘油诱导的肌肉损伤具有不同的敏感性,并且使用ASC治疗神经肌肉疾病需要进一步仔细评估。

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