Steadman Philippon Research Institute, Vail, CO, USA.
Department of Orthopaedic Surgery, The University of Texas Health Science Center at Houston, Houston, TX, USA.
FASEB J. 2021 Mar;35(3):e21378. doi: 10.1096/fj.202001914R.
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.
肌肉再生能力随年龄下降归因于肌肉祖细胞（MPC）反应性降低。异时性联体已被用作研究衰老对干细胞及其生态位影响的模型。这些研究表明，通过使老年小鼠暴露于年轻的全身环境中，可以使老年祖细胞年轻化。一个有趣的观点是，妊娠代表了一种独特的生物学模型，即在发育和成熟生物体之间存在自然共享的循环系统。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，基于改善的肌肉组织学、更好的肌肉再生以及炎症和坏死的减少。此外，我们发现与非妊娠小鼠的 MPC 相比，来自妊娠小鼠的 MPC 在体外显示出明显改善的成肌分化能力和体内肌肉再生能力。此外，当在来自妊娠小鼠的血清存在下培养时，非妊娠小鼠的 MPC 显示出增强的成肌能力。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，以增强祖细胞的成肌潜能和肌肉修复。
