Department of Biotechnology, CHA University, 13488, Seongnam, Korea.
Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 13496, Seongnam, Korea.
J Muscle Res Cell Motil. 2024 Jun;45(2):53-68. doi: 10.1007/s10974-023-09643-7. Epub 2023 Feb 18.
Muscle atrophy significantly impairs health and quality of life; however, there is still no cure. Recently, the possibility of regeneration in muscle atrophic cells was suggested through mitochondrial transfer. Therefore, we attempted to prove the efficacy of mitochondrial transplantation in animal models. To this end, we prepared intact mitochondria from umbilical cord-derived mesenchymal stem cells maintaining their membrane potential. To examine the efficacy of mitochondrial transplantation on muscle regeneration, we measured muscle mass, cross-sectional area of muscle fiber, and changes in muscle-specific protein. In addition, changes in the signaling mechanisms related to muscle atrophy were evaluated. As a result, in mitochondrial transplantation, the muscle mass increased by 1.5-fold and the lactate concentration decreased by 2.5-fold at 1 week in dexamethasone-induced atrophic muscles. In addition, a 2.3-fold increase in the expression of desmin protein, a muscle regeneration marker, showed a significant recovery in MT 5 µg group. Importantly, the muscle-specific ubiquitin E3-ligases MAFbx and MuRF-1 were significantly decreased through AMPK-mediated Akt-FoxO signaling pathway by mitochondrial transplantation compared with the saline group, reaching a level similar to that in the control. Based on these results, mitochondrial transplantation may have therapeutic applications in the treatment of atrophic muscle disorders.
肌肉萎缩显著损害健康和生活质量；然而，目前仍然没有治愈方法。最近，通过线粒体转移，肌肉萎缩细胞再生的可能性被提出。因此，我们试图通过动物模型证明线粒体移植的疗效。为此，我们从脐带间充质干细胞中制备了保持膜电位完整的线粒体。为了检验线粒体移植对肌肉再生的疗效，我们测量了肌肉质量、肌纤维横截面积和肌肉特异性蛋白的变化。此外，还评估了与肌肉萎缩相关的信号机制的变化。结果表明，在皮质酮诱导的萎缩肌肉中，线粒体移植后第 1 周，肌肉质量增加了 1.5 倍，乳酸浓度降低了 2.5 倍。此外，肌生成标志物结蛋白表达增加了 2.3 倍，表明 MT 5μg 组有显著恢复。重要的是，与生理盐水组相比，通过线粒体移植，AMPK 介导的 Akt-FoxO 信号通路使肌肉特异性泛素 E3 连接酶 MAFbx 和 MuRF-1 显著减少，达到与对照组相似的水平。基于这些结果，线粒体移植可能在治疗萎缩性肌肉疾病方面具有治疗应用。
