Park Sang Eon, Jeong Jang Bin, Oh Shin Ji, Kim Sun Jeong, Kim Hyeongseop, Choi Alee, Choi Suk-Joo, Oh Soo-Young, Ryu Gyu Ha, Lee Jeehun, Jeon Hong Bae, Chang Jong Wook
Stem Cell Institute, ENCell Co., Ltd., Seoul 06072, Korea.
Samsung Medical Center, Stem Cell & Regenerative Medicine Institute, Seoul 06351, Korea.
Biomedicines. 2021 Aug 26;9(9):1089. doi: 10.3390/biomedicines9091089.
The aim of this study was to evaluate the therapeutic effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3-5 months old) were administered five different doses of WJ-MSCs through their tail veins. A week after injection, grip strength measurements, creatine kinase (CK) assays, immunohistochemistry, and western blots were performed for comparison between healthy mice, mdx control mice, and WJ-MSC-injected mdx mice. WJ-MSCs exerted dose-dependent multisystem therapeutic effects in mdx mice, by decreasing CK, recovering normal behavior, regenerating muscle, and reducing apoptosis and fibrosis in skeletal muscle. We also confirmed that miR-499-5p is significantly downregulated in mdx mice, and that intravenous injection of WJ-MSCs enhanced its expression, leading to anti-fibrotic effects via targeting TGFβR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic "off-the-shelf" cellular products for the treatment of DMD and possibly other muscle disorders.
本研究的目的是评估沃顿胶源间充质干细胞（WJ-MSCs）在杜氏肌营养不良症（DMD）动物模型中的治疗效果及机制。将3至5月龄的mdx小鼠通过尾静脉注射五种不同剂量的WJ-MSCs。注射一周后，进行握力测量、肌酸激酶（CK）检测、免疫组织化学和蛋白质印迹分析，以比较健康小鼠、mdx对照小鼠和注射WJ-MSCs的mdx小鼠。WJ-MSCs在mdx小鼠中发挥了剂量依赖性的多系统治疗作用，包括降低CK水平、恢复正常行为、使肌肉再生以及减少骨骼肌中的细胞凋亡和纤维化。我们还证实，miR-499-5p在mdx小鼠中显著下调，静脉注射WJ-MSCs可增强其表达，通过靶向TGFβR 1和3产生抗纤维化作用。因此，WJ-MSCs可能代表用于治疗DMD以及可能的其他肌肉疾病的新型异基因“现成”细胞产品。
