Enhancement of myogenic potential of muscle progenitor cells and muscle healing during pregnancy.
Enhancement of myogenic potential of muscle progenitor cells and muscle healing during pregnancy.
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增强妊娠期间肌肉祖细胞的生肌潜力和肌肉愈合。
DOI：
10.1096/fj.202001914r
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Huard,Johnny
中科院分区：
文献类型：
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作者：
Lu,Aiping;Guo,Ping;Pan,Haiying;Tseng,Chieh;Sinha,KrishnaM;Yang,Fan;Scibetta,Alex;Cui,Yan;Huard,Matthieu;Zhong,Ling;Ravuri,Sudheer;Huard,Johnny
随着年龄的增长，肌肉再生潜力的下降归因于肌肉祖细胞（MPCs）的反应性减弱。异时共生已被用作研究衰老对干细胞及其生态位的影响的模型。这些研究表明，通过将老年小鼠暴露于年轻的全身环境，可以使老年祖细胞恢复活力。一个有趣的想法是，怀孕代表了发育和成熟生物体之间自然共享循环系统的独特生物学模型。为了验证这一假设，我们使用心脏毒素（CTX）损伤小鼠模型评估了妊娠小鼠的肌肉再生潜力。我们的研究结果表明，与非妊娠对照小鼠相比，妊娠小鼠在肌肉损伤后表现出加速的肌肉愈合，这是基于肌肉组织学的改善、上级肌肉再生以及炎症和坏死的减少。此外，我们发现与来自非妊娠小鼠的MPC相比，从妊娠小鼠中分离的MPC在体外生肌分化能力和体内肌肉再生方面表现出显着改善。此外，当在从妊娠小鼠获得的血清存在下培养时，来自非妊娠小鼠的MPC显示出增强的生肌能力。我们从这些研究中获得的蛋白质组学数据提供了潜在的治疗靶点，以增强祖细胞和肌肉修复的成肌潜力。
The decline of muscle regenerative potential with age has been attributed to a diminished responsiveness of muscle progenitor cells (MPCs). Heterochronic parabiosis has been used as a model to study the effects of aging on stem cells and their niches. These studies have demonstrated that, by exposing old mice to a young systemic environment, aged progenitor cells can be rejuvenated. One interesting idea is that pregnancy represents a unique biological model of a naturally shared circulatory system between developing and mature organisms. To test this hypothesis, we evaluated the muscle regeneration potential of pregnant mice using a cardiotoxin (CTX) injury mouse model. Our results indicate that the pregnant mice demonstrate accelerated muscle healing compared to nonpregnant control mice following muscle injury based on improved muscle histology, superior muscle regeneration, and a reduction in inflammation and necrosis. Additionally, we found that MPCs isolated from pregnant mice display a significant improvement of myogenic differentiation capacity in vitro and muscle regeneration in vivo when compared to the MPCs from nonpregnant mice. Furthermore, MPCs from nonpregnant mice display enhanced myogenic capacity when cultured in the presence of serum obtained from pregnant mice. Our proteomics data from these studies provides potential therapeutic targets to enhance the myogenic potential of progenitor cells and muscle repair.