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临床级人脐带间充质干细胞改善与年龄相关的肌肉减少症小鼠的骨骼肌功能障碍。

Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice.

机构信息

Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Cell Death Dis. 2023 May 12;14(5):321. doi: 10.1038/s41419-023-05843-8.

Abstract

With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.

摘要

随着人口老龄化的扩张,与年龄相关的肌肉减少症(AAS)已成为老年人严重的临床疾病,也是健康老龄化的关键挑战。遗憾的是,目前尚无针对 AAS 的批准疗法。在这项研究中,临床级人脐带间充质干细胞(hUC-MSCs)被用于两种经典的小鼠模型(SAMP8 小鼠和 D-半乳糖诱导的衰老小鼠),通过行为测试、免疫染色和 Western blot 研究了其对骨骼肌质量和功能的影响。核心数据结果表明,hUC-MSCs 通过提高关键细胞外基质蛋白的表达、激活卫星细胞、增强自噬和阻止细胞衰老等机制,显著恢复了两种小鼠模型的骨骼肌力量和性能。该研究首次全面评估和展示了临床级 hUC-MSCs 在两种小鼠模型中治疗 AAS 的临床前疗效,不仅为 AAS 提供了一种新的模型,而且突出了一种改善和治疗 AAS 及其他与年龄相关的肌肉疾病的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d5/10182022/f4079b2ddd50/41419_2023_5843_Figa_HTML.jpg

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