Vilquin J T, Wagner E, Kinoshita I, Roy R, Tremblay J P
Centre de Recherche en Neurobiologie de l'Université Laval, Hôpital de l'Enfant-Jésus, Québec, Canada.
J Cell Biol. 1995 Nov;131(4):975-88. doi: 10.1083/jcb.131.4.975.
Myoblast transplantation has been considered a potential treatment for some muscular disorders. It has proven very successful, however, only in immunodeficient or immunosuppressed mice. In this study, myoblasts from C57BL10J +/+ mice were transplanted, with no immunosuppressive treatment, in the tibialis anterior of fully histocompatible but dystrophin-deficient C57BL10J mdx/mdx mice. One to 9 months after transplantation, the success of the graft was evaluated by immunohistochemistry. All the transplanted mice (n = 24) developed dystrophin-positive fibers following transplantation. Depending on myoblast cultures, transplantations, and time of analysis, the mice presented 15 to 80% of dystrophin-positive fibers in transplanted muscles. These fibers were correctly oriented and they were either from donor or hybrid origin. The dystrophin-positive fibers remained stable up to 9 months. Possible humoral and cellular immune responses were investigated after grafting. Antibodies directed against dystrophin and/or muscle membrane were developed by 58% of the mice as demonstrated by immunohistochemistry and Western blotting. Despite the presence of these antibodies, dystrophin-positive fibers were still present in grafted muscles 9 months after transplantation. Moreover, the muscles did not show massive infiltration by CD4 cells, CD8 cells, or macrophages, as already described in myoblast allotransplantations. This lack of rejection was attributed to the sequestrated nature of dystrophin after fiber formation. These results indicate that myoblast transplantation leads to fiber formation when immunocompetent but fully histocompatible donors and recipients are used and that dystrophin incompatibility alone is not sufficient to induce an immunological rejection reaction.
成肌细胞移植已被视为治疗某些肌肉疾病的一种潜在方法。然而，事实证明，它仅在免疫缺陷或免疫抑制的小鼠中非常成功。在本研究中，将来自C57BL10J +/+小鼠的成肌细胞在不进行免疫抑制治疗的情况下，移植到组织相容性完全匹配但缺乏抗肌萎缩蛋白的C57BL10J mdx/mdx小鼠的胫前肌中。移植后1至9个月，通过免疫组织化学评估移植的成功率。所有移植的小鼠（n = 24）在移植后均出现了抗肌萎缩蛋白阳性纤维。根据成肌细胞培养、移植情况和分析时间，这些小鼠移植肌肉中的抗肌萎缩蛋白阳性纤维占15%至80%。这些纤维方向正确，它们要么来自供体，要么是杂种起源。抗肌萎缩蛋白阳性纤维在长达9个月的时间内保持稳定。移植后研究了可能的体液和细胞免疫反应。免疫组织化学和蛋白质印迹法显示，58%的小鼠产生了针对抗肌萎缩蛋白和/或肌膜的抗体。尽管存在这些抗体，但移植后9个月，移植肌肉中仍存在抗肌萎缩蛋白阳性纤维。此外，肌肉并未像在成肌细胞同种异体移植中所描述的那样，出现CD4细胞、CD8细胞或巨噬细胞的大量浸润。这种缺乏排斥反应的现象归因于纤维形成后抗肌萎缩蛋白的隔离性质。这些结果表明，当使用具有免疫活性但组织相容性完全匹配的供体和受体时，成肌细胞移植可导致纤维形成，并且仅抗肌萎缩蛋白不相容不足以诱导免疫排斥反应。
