Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N1EH, UK.
NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London, WC1N 1EH, UK.
Sci Rep. 2020 Jul 6;10(1):11119. doi: 10.1038/s41598-020-68098-9.
Skeletal muscle stem (satellite) cells transplanted into host mouse muscles contribute to muscle regeneration. Irradiation of host muscle enhances donor stem cell engraftment by promoting the proliferation of transplanted donor cells. We hypothesised that, similar to other systems, cells damaged by radiation might be effecting this donor cell proliferation. But we found no difference in the percentage of dying (TUNEL+) cells in immunodeficient dystrophic mouse muscles at the times after the irradiation dose that enhances donor cell engraftment. Similarly, irradiation did not significantly increase the number of TUNEL+ cells in non-dystrophic immunodeficient mouse muscles and it only slightly enhanced donor satellite cell engraftment in this mouse strain, suggesting either that the effector cells are present in greater numbers within dystrophic muscle, or that an innate immune response is required for effective donor cell engraftment. Donor cell engraftment within non-irradiated dystrophic host mouse muscles was not enhanced if they were transplanted with either satellite cells, or myofibres, derived from irradiated dystrophic mouse muscle. But a mixture of cells from irradiated muscle transplanted with donor satellite cells promoted donor cell engraftment in a few instances, suggesting that a rare, yet to be identified, cell type within irradiated dystrophic muscle enhances the donor stem cell-mediated regeneration. The mechanism by which cells within irradiated host muscle promote donor cell engraftment remains elusive.
骨骼肌干细胞(卫星)移植到宿主肌肉中有助于肌肉再生。宿主肌肉的辐照通过促进移植供体细胞的增殖来增强供体干细胞的植入。我们假设,类似于其他系统,辐射损伤的细胞可能会影响供体细胞的增殖。但是,我们没有发现在增强供体细胞植入的辐照剂量后,免疫缺陷型营养不良小鼠肌肉中死亡(TUNEL+)细胞的百分比有差异。同样,辐照并没有显著增加非营养不良免疫缺陷型小鼠肌肉中 TUNEL+细胞的数量,而且它只略微增强了这种小鼠品系中供体卫星细胞的植入,这表明效应细胞在营养不良的肌肉中数量更多,或者需要先天免疫反应才能有效地进行供体细胞植入。如果将源自辐射性营养不良小鼠肌肉的卫星细胞或肌纤维移植到未辐照的营养不良宿主小鼠肌肉中,则不会增强供体细胞的植入。但是,将来自辐照肌肉的细胞混合物与供体卫星细胞一起移植,在少数情况下会促进供体细胞的植入,这表明辐照性营养不良肌肉中存在一种罕见的、尚未确定的细胞类型,可增强供体干细胞介导的再生。辐射宿主肌肉内的细胞促进供体细胞植入的机制仍然难以捉摸。