Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Sci Transl Med. 2010 Nov 10;2(57):57ra83. doi: 10.1126/scitranslmed.3001081.
Skeletal muscle is dynamic, adapting to environmental needs, continuously maintained, and capable of extensive regeneration. These hallmarks diminish with age, resulting in a loss of muscle mass, reduced regenerative capacity, and decreased functionality. Although the mechanisms responsible for this decline are unclear, complex changes within the local and systemic environment that lead to a reduction in regenerative capacity of skeletal muscle stem cells, termed satellite cells, are believed to be responsible. We demonstrate that engraftment of myofiber-associated satellite cells, coupled with an induced muscle injury, markedly alters the environment of young adult host muscle, eliciting a near-lifelong enhancement in muscle mass, stem cell number, and force generation. The abrogation of age-related atrophy appears to arise from an increased regenerative capacity of the donor stem cells, which expand to occupy both myonuclei in myofibers and the satellite cell niche. Further, these cells have extensive self-renewal capabilities, as demonstrated by serial transplantation. These near-lifelong, physiological changes suggest an approach for the amelioration of muscle atrophy and diminished function that arise with aging through myofiber-associated satellite cell transplantation.
骨骼肌具有动态适应性，能够根据环境需求进行不断的维护和广泛的再生。这些特征随着年龄的增长而减弱，导致肌肉质量减少、再生能力降低和功能下降。尽管导致这种衰退的机制尚不清楚，但人们认为，导致骨骼肌干细胞（称为卫星细胞）再生能力下降的局部和全身环境的复杂变化是造成这种情况的原因。我们证明，与诱导的肌肉损伤相结合的肌纤维相关卫星细胞的移植，显著改变了年轻成年宿主肌肉的环境，引发了肌肉质量、干细胞数量和力量生成的近乎终生增强。与年龄相关的萎缩的消除似乎源于供体干细胞再生能力的增强，这些细胞扩增以占据肌纤维中的肌细胞核和卫星细胞龛。此外，这些细胞具有广泛的自我更新能力，正如通过连续移植所证明的那样。这些近乎终生的生理变化表明，通过肌纤维相关卫星细胞移植来改善衰老引起的肌肉萎缩和功能减退是一种可行的方法。
