Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, El-Khalyfa El-Mamoun Street Abbasya, Cairo, Egypt.
Tissue Eng Regen Med. 2020 Dec;17(6):887-900. doi: 10.1007/s13770-020-00288-y. Epub 2020 Oct 8.
Skeletal muscle injuries are frequent clinical challenges due to associated fibrosis and disability. Regenerative medicine is an emerging promising strategy for such cases. The aim of this study was to compare between the effects of bone marrow-mesenchymal stem cells (BM-MSCs) versus adipose tissue stromal cells (ADSCs) on regeneration and re-innervation of skeletal muscle laceration injury in Wistar rats at different time intervals.
Six young male rats were used as a source of allogenic MSCs. Eighty-four adult female rats were divided into: Group I (control), Group II (Untreated Laceration): right gluteal muscle was lacerated and left for spontaneous healing, Group III (BM-MSCs): right gluteal muscle was lacerated with concomitant local intramuscular injection of 1 × 10 BM-MSCs in the lacerated muscle, Group IV (ADSCs): right gluteal muscle was lacerated with concomitant local intramuscular injection of 1 × 10 ADSCs in lacerated muscle. Rats were sacrificed after one, two and eight weeks. Muscles were processed to prepare sections stained with H&E, Mallory's trichrome and immune-histochemical staining (neurofilament light chain).
A significant increase in collagen fibers and failure of re-innervation were noticed in untreated laceration group. BM-MSCs-treated groups showed regeneration of muscle fibers but with increased collagen fibers. Meanwhile, ADSCs showed better regenerative effects evidenced by significant increase in the number of myotubes and significant decrease in collagen deposition. Re-innervation was noticed in MSCs-injected muscles after 8 weeks of laceration.
Both BM-MSCs and ADSCs improved regeneration of skeletal muscle laceration injury at short- and long-term durations. However, fibrosis was less in ADSCs-treated rats. Effective re-innervation of injured muscles occurred only at the long-term duration.
骨骼肌损伤是常见的临床挑战,其常伴有纤维化和残疾。再生医学是治疗此类疾病的新兴有前途的策略。本研究的目的是比较骨髓间充质干细胞(BM-MSCs)与脂肪组织基质细胞(ADSCs)对 Wistar 大鼠骨骼肌裂伤后不同时间间隔的再生和再神经支配的影响。
6 只雄性大鼠作为同种异体 MSC 的来源。84 只成年雌性大鼠分为:I 组(对照组),II 组(未治疗的裂伤):右臀肌裂伤,自行愈合;III 组(BM-MSCs):右臀肌裂伤,同时在裂伤肌肉内局部肌肉内注射 1×10 BM-MSCs;IV 组(ADSCs):右臀肌裂伤,同时在裂伤肌肉内局部肌肉内注射 1×10 ADSCs。大鼠在 1、2 和 8 周后处死。肌肉经处理制备 H&E、Mallory 三色和免疫组织化学染色(神经丝轻链)切片。
未治疗的裂伤组胶原纤维明显增加,再神经支配失败。BM-MSCs 治疗组的肌纤维再生,但胶原纤维增加。同时,ADSCs 表现出更好的再生效果,表现为肌管数量显著增加,胶原沉积显著减少。裂伤 8 周后,在 MSC 注射肌肉中观察到再神经支配。
BM-MSCs 和 ADSCs 均可改善骨骼肌裂伤的短期和长期再生。然而,ADSCs 治疗组的纤维化较少。只有在长期时程,损伤肌肉才能有效再神经支配。