Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation.
Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Early Skeletal Muscle Tissue Formation.
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DOI：
10.3727/096368917x694868
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发表时间：
2017-06-09
影响因子：
3.3
通讯作者：
Eberli D
中科院分区：
文献类型：
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作者：
Haralampieva D;Salemi S;Dinulovic I;Sulser T;Ametamey SM;Handschin C;Eberli D
肌肉前体细胞(MPC)是一种激活的卫星细胞，能够重建肌肉纤维。因此，自体MPC移植有望用于肌肉疾病的治疗。然而，随着年龄的增长，MPC的密度以及它们的增殖和分化潜能逐渐下降。本研究的目的是通过基因修饰人巨噬细胞，使其过表达作为运动适应关键调节因子的过氧化物酶体增殖物激活受体γ共激活因子(PGC-1α)，从而提高早期骨骼肌的形成和质量。我们能够确认转基因hMPC的持续肌源性表型。在保持其活性和增殖能力的同时，pGC-1α修饰的hMPC在体外显示出更强的肌纤维形成能力。皮下注射细胞-胶原悬液后1、2、4周取材，组织学分析证实pGC-1α修饰样品较早形成肌管，主要为慢抽动肌纤维。Western Blot检测到心肌收缩蛋白水平升高。综上所述，通过基因修饰hMPC来过表达PGC-1α，我们能够在体外和体内促进早期肌纤维的形成，最初转变为慢型肌纤维。因此，高表达PGC-1α是进一步增强骨骼肌组织工程的新策略。
Muscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential gradually decline with age. The goal of this research was to genetically modify human MPCs (hMPCs) to overexpress the peroxisome proliferator-activated receptor gamma coactivator (PGC-1α), a key regulator of exercise-mediated adaptation, and thereby to enhance early skeletal muscle formation and quality. We were able to confirm the sustained myogenic phenotype of the genetically modified hMPCs. While maintaining their viability and proliferation potential, PGC-1α modified hMPCs showed an enhanced myofiber formation capacity in vitro. Engineered muscle tissues were harvested 1, 2 and 4 weeks after subcutaneous injection of cell-collagen suspensions and histological analysis confirmed the earlier myotube formation in PGC-1α modified samples, predominantly of slow twitch myofibers. Increased contractile protein levels were detected by Western Blot. In summary, by genetically modifying hMPCs to overexpress PGC-1α we were able to promote early muscle fiber formation in vitro and in vivo, with an initial switch to slow type myofibers. Therefore, overexpressing PGC-1α is novel strategy to further enhance skeletal muscle tissue engineering.