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Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage.
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-05-20 , DOI: 10.3389/fnmol.2020.00107
Matteo Rigon 1 , Sarah Janice Hörner 1 , Tatjana Straka 1 , Karen Bieback 2 , Norbert Gretz 3, 4 , Mathias Hafner 1, 4 , Rüdiger Rudolf 1, 4, 5
Affiliation  

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.



中文翻译:

ASC施用对甘油诱导的肌肉损伤后终板再生的影响。

在其他方法中,最近已测试了脂肪来源的基质细胞(ASC)的再生能力,可用于治疗神经肌肉疾病。尽管先前已经观察到ASC对肌肉恢复的有益作用,但它们对神经肌肉接头(NMJ)再生的影响尚不清楚。在这里,我们使用了鼠类甘油损伤模型来研究NMJ的破坏和再生,并评估ASC全身应用对肌肉和NMJ恢复的影响。在未用ASC治疗的小鼠中,观察到突触前和突触后NMJ对甘油诱导的损伤的不同反应。虽然在坏死的,缺乏肌动蛋白和肌营养不良蛋白的区域中仍然存在突触后,但是在那些受影响的地区突触前很快消失了。损伤后11天内发生了NMJ的部分再生。ASC治疗略微增强了NMJ的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晚期。总之,结果表明突触前和突触后NMJ对甘油诱导的肌肉损伤的敏感性不同,使用ASC治疗神经肌肉疾病需要进一步仔细评估。

更新日期:2020-06-23
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