Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1

International Journal of Molecular Sciences

GyuHa Ryu¹  Soo-young Oh²  Suk-joo Choi²  Jeehun Lee³  JongWook Chang⁴  Alee Choi⁴  JangBin Jeong⁴  SangEon Park⁴  HongBae Jeon⁴ 

[1] Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University School of Medicine, Seoul 06351, Korea;Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul 06351, Korea;Department of Pediatrics, Samsung Medical Center, Seoul 06351, Korea;Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea;

关键词: Duchenne muscular dystrophy;    matrix metalloproteinase-1;    paracrine factor;    skeletal muscle fibrosis;    Wharton’s jelly-derived mesenchymal stem cell;   

DOI  :  10.3390/ijms21176269

来源: DOAJ

【 摘 要 】

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 10⁵ Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

【 授权许可】

Unknown