HIGH-EFFICIENCY OF MUSCLE REGENERATION AFTER HUMAN MYOBLAST CLONE TRANSPLANTATION IN SCID MICE

被引:133
作者
HUARD, J
VERREAULT, S
ROY, R
TREMBLAY, M
TREMBLAY, JP
机构
[1] HOP ENFANTS JESUS, CTR RECH NEUROBIOL, QUEBEC CITY G1J 1Z4, PQ, CANADA
[2] UNIV LAVAL, CTR HOSP, CTR RECH INFLAMMAT IMMUNOL & RHEUMATOL, ST FOY G1V 4G2, PQ, CANADA
关键词
MUSCULAR DYSTROPHY; MOUSE; IMMUNITY; TRANSPLANTATION IMMUNOLOGY; MUSCLES;
D O I
10.1172/JCI117011
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
SCID mouse tibialis anterior muscles were first irradiated to prevent regeneration by host myoblasts and injected with notexin to damage the muscle fibers and trigger regeneration. The muscles were then injected with roughly 5 million human myoblasts. 1 mo later, 16-33% of the normal number of muscle fibers were present in the injected muscle, because of incomplete regeneration. Hwoever, > 90% of these muscle fibers contained human dystrophin. Some newly formed muscle fibers had an accumulation of human dystrophin and desmin on a part of their membrane. Such accumulations have been demonstrated at neuromuscular junctions before suggesting that the new muscle fibers are innervated and functional. The same pool of clones of human myoblasts produced only less than or equal to 4% of muscle fibers containing human dystrophin when injected in nude mice muscles. Several of the human myoblasts did not fuse and remained in interstial space or tightly associated with muscle fibers suggesting that some of them have formed satellite cells. Moreover, cultures of 98% pure human myoblasts were obtained from transplanted SCID muscles: In some mice where the muscle regeneration was not complete, the muscle fibers containing human dystrophin also expressed uniformly HLA class 1, confirming that the fibers are of human origin. The presence of hybrid muscle fibers containing human dystrophin and mouse MHC was also demonstrated following transplantation. These results establish that in absence of an immune reaction, transplanted human myoblasts participate to the muscle regeneration with a high degree of efficacy even if the animals were killed only 1 mo after the transplantation.
引用
收藏
页码:586 / 599
页数:14
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