Myogenic Stem Cell Function in Aging Skeletal Muscle

描述(申请人提供)：骨骼肌质量、力量和再生能力随着年龄的增长而下降。促进成肌前体细胞在衰老肌肉中的增殖可以提高肌纤维修复的效率，从而减少与年龄相关的肌肉萎缩。因此，识别能够增强衰老肌肉中肌源性前体功能的生理剂具有重要意义。卫星细胞(位于肌纤维表面)被认为是出生后肌肉中的成肌前体细胞。虽然卫星细胞通常作为组织特异性肌源性干细胞发挥作用，但最近从成人肌肉中分离出了能够产生肌源性细胞的多潜能干细胞。深入了解成年肌和衰老骨骼肌中肌源性前体的起源以及这些前体所衍生的细胞类型，可以进一步帮助设计治疗方案，以改善衰老肌肉中肌源性前体的数量和功能。本研究的目的是：1)研究成纤维细胞生长因子(FGF2)对衰老肌肉卫星细胞增殖的影响。2)研究成年和老年啮齿动物血管来源的细胞向骨骼肌源性前体细胞分化的可能性。3)检测血管来源的细胞在体内参与肌纤维修复的能力。老鼠将在整个调查过程中使用。在分离的肌纤维培养中，将分析成纤维细胞生长因子对卫星细胞增殖的影响。血管系统产生骨骼肌源性细胞的能力将用来自骨骼肌和非骨骼肌来源的血管进行检测。血管来源的细胞将在克隆培养中通过免疫细胞化学和RT-PCR进行鉴定。体内研究将检验来自血管系统的细胞在Dystrophin缺陷的MDX裸鼠的宿主肌肉中贡献肌纤维核和卫星细胞的能力。这项拟议的研究将有助于对成年肌和衰老肌肉中肌源性前体的状态进行新的洞察，并可能被证明对疾病和衰老期间的肌肉康复策略具有重要意义。

DESCRIPTION (provided by applicant): Skeletal muscle mass, strength and regenerative capacity decline with aging. Enhanced proliferation of myogenic precursor cells in aging muscle could improve the efficiency of myofiber repair and lead to a reduction in age-linked muscle atrophy. Thus, the identification of physiological agents capable of enhancing the function of myogenic precursors in the aging muscle is of significant importance. Satellite cells (located on the surface of the myofiber) are well recognized as the myogenic precursors in postnatal muscle. While satellite cells typically function as tissue-specific myogenic stem cells, multipotent stem cells, capable of giving rise to myogenic cells, have been recently isolated from adult muscle. Gaining insight into the origins of myogenic precursors in adult and aging skeletal muscle as well as the types of cells derived from these precursors can further assist in the design of therapies to improve the number and function of myogenic precursors in aging muscle. The aims of this proposal are: 1) To investigate the effect of fibroblast growth factor (FGF2) on the proliferation of satellite cells in aging muscle. 2) To investigate the potential of cells derived from the vasculature of adult and aging rodents to give rise to skeletal myogenic precursors. 3) To examine the capacity of cells derived from the vasculature to participate in myofiber repair in vivo. Mice will be used throughout the investigations. The effect of FGF on the proliferation of satellite cells will be analyzed in cultures of isolated myofibers. The capacity of the vasculature to give rise to skeletal myogenic cells will be examined with vessels from skeletal muscle and non-skeletal muscle origins. The vasculature-derived cells will be characterized in clonal cultures by immunocytochemistry and RT-PCR. The in vivo studies will examine the ability of cells derived from the vasculature to contribute myofiber nuclei and satellite cells in host muscle of dystrophin-deficient mdx nude mice. The proposed investigation will contribute new insight into the status of myogenic precursors in the adult and aging muscle and can prove important for muscle rehabilitation strategies during disease and aging.