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脂肪组织来源的间充质干细胞外泌体促进骨骼肌再生。

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells.

机构信息

Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Gyeonggi-do 13488, Korea.

CHA Graduate School of Medicine, 120 Hyeryong-ro, Pocheon 11160, Korea.

出版信息

Curr Issues Mol Biol. 2021 Oct 9;43(3):1473-1488. doi: 10.3390/cimb43030104.

Abstract

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control ( = 4), muscle defect ( = 6), and muscle defect + exosome ( = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

摘要

严重的骨骼肌损失可导致严重的残疾和美容畸形。间充质干细胞(MSC)衍生的外泌体已显示出作为组织再生有效治疗工具的潜力。本研究旨在确定 MSC 衍生的外泌体对骨骼肌再生的再生能力。从人脂肪组织来源的 MSC(AD-MSC)中分离出外泌体。使用细胞活力、相关基因和蛋白质分析研究 MSC 衍生的外泌体对卫星细胞的影响。此外,使用 NOD-SCID 小鼠并将其随机分配到健康对照组( = 4)、肌肉缺损组( = 6)和肌肉缺损+外泌体组( = 6)。通过在后肢的四头肌上使用活检冲孔来创建肌肉缺损。手术后 4 周,采集、称重和组织学分析四头肌。MSC 衍生的外泌体处理增加了肌细胞相关基因的增殖和表达,肌生成素的免疫荧光分析也显示出类似的趋势。组织学上,MSC 衍生的外泌体处理组的肌束形状和大小相对保存完好。免疫组织化学染色显示 MSC 衍生的外泌体处理组中肌生成素和成肌决定蛋白 1 的表达更高。这些结果表明,从 AD-MSC 中提取的外泌体具有骨骼肌再生的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1da/8929094/bac62ce40917/cimb-43-00104-g001.jpg

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