The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom.
Stem Cells. 2012 Sep;30(9):1971-84. doi: 10.1002/stem.1158.
Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy.
干细胞移植已经在某些遗传疾病的临床实践中得到应用，并且是治疗肌肉营养不良的有前途的疗法。我们使用 Duchenne 肌营养不良症的 mdx 小鼠模型研究了宿主卫星细胞生态位对供体肌肉干细胞（卫星细胞）对肌肉再生的贡献的影响。我们发现，宿主卫星细胞的失能和肌肉生态位的保留促进了供体卫星细胞对肌肉再生和卫星细胞隔室的功能重建的贡献。但是，如果宿主生态位没有及时填充，或者被有能力的宿主卫星细胞填充，则它变得无功能，并且供体植入物可以忽略不计。将该方案应用于老年宿主肌肉也促进了来自老年供体卫星细胞的有效再生。相比之下，如果生态位被破坏，但宿主卫星细胞仍然具有增殖能力，则供体衍生的植入物微不足道。因此，保留卫星细胞生态位，同时使大多数在营养不良的人类肌肉中功能失调的卫星细胞失能，可能会提高干细胞治疗的效率。
