Bouchentouf Manaf, Benabdallah Basma F, Mills Philippe, Tremblay Jacques P
CHUQ-CHUL, Laval University, 2705 boulevard Laurier, Ste-Foy, G1V4G2 Canada.
Neuromuscul Disord. 2006 Aug;16(8):518-29. doi: 10.1016/j.nmd.2006.06.003. Epub 2006 Aug 21.
Transplantation of normal muscle precursor cells is a potential approach to restore dystrophin expression within dystrophin [deficient] mdx mice, a model of Duchenne Muscular Dystrophy. This study aims to evaluate whether exercise could improve graft success and hybrid fiber distribution within mdx muscle. eGFP(+) Muscle precursor cells were transplanted into tibialis anterior muscles of mdx mice using a single injection trajectory. During the following weeks, muscle fiber breaks were induced by making mdx mice swim. To evaluate fiber damage, Evans blue solution was injected intraperitoneally to mice 16h before their sacrifice. Tibialis anterior muscles were then harvested and eGFP, dystrophin and Evans blue labeling were analyzed by fluorescent microscopy. Twenty minutes of exercise (i.e., swimming) were used to induce damage in about 30% of TA muscle fibers. Graft success, evaluated as the percentage of hybrid fibers which are eGFP(+), was improved by 1.9-fold after swimming 3 times per week during 4 weeks and by 1.8-fold after daily swimming. Hybrid muscle fiber transversal and longitudinal distribution were also increased after repeated physical efforts. Exercise induced fiber breaks, which improved MPC recruitment and fusion and increased long-term graft success and also transverse and longitudinal distribution of hybrid fibers.
移植正常肌肉前体细胞是恢复杜氏肌营养不良症模型——肌营养不良蛋白缺陷mdx小鼠体内肌营养不良蛋白表达的一种潜在方法。本研究旨在评估运动是否能提高mdx小鼠肌肉内的移植成功率和杂种纤维分布。使用单一注射轨迹将eGFP(+)肌肉前体细胞移植到mdx小鼠的胫前肌中。在接下来的几周里，通过让mdx小鼠游泳诱导肌肉纤维断裂。为了评估纤维损伤情况，在处死小鼠前16小时腹腔注射伊文思蓝溶液。然后收获胫前肌，并通过荧光显微镜分析eGFP、肌营养不良蛋白和伊文思蓝标记情况。20分钟的运动（即游泳）使约30%的胫前肌纤维受到损伤。以eGFP(+)杂种纤维的百分比来评估，每周游泳3次，持续4周后移植成功率提高了1.9倍，每日游泳后提高了1.8倍。反复进行体力活动后，杂种肌纤维的横向和纵向分布也增加了。运动诱导纤维断裂，这改善了肌肉前体细胞的募集和融合，提高了长期移植成功率，还增加了杂种纤维的横向和纵向分布。
