Dell'Agnola Chiara, Wang Zejing, Storb Rainer, Tapscott Stephen J, Kuhr Christian S, Hauschka Stephen D, Lee Richard S, Sale George E, Zellmer Eustacia, Gisburne Serina, Bogan Janet, Kornegay Joe N, Cooper Barry J, Gooley Theodore A, Little Marie-Térèse
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Blood. 2004 Dec 15;104(13):4311-8. doi: 10.1182/blood-2004-06-2247. Epub 2004 Aug 24.
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene on the X-chromosome that result in skeletal and cardiac muscle damage and premature death. Studies in mice, including the mdx mouse model of DMD, have demonstrated that circulating bone marrow-derived cells can participate in skeletal muscle regeneration, but the potential clinical utility of treating human DMD by allogeneic marrow transplantation from a healthy donor remains unknown. To assess whether allogeneic hematopoietic cell transplantation (HCT) provides clinically relevant levels of donor muscle cell contribution in dogs with canine X-linked muscular dystrophy (c-xmd), 7 xmd dogs were given hematopoietic cell (HC) transplants from nonaffected littermates. Compared with the pretransplantation baseline, the number of dystrophin-positive fibers and the amount of wild-type dystrophin RNA did not increase after HCT, with observation periods ranging from 28 to 417 days. Similar results were obtained when the recipient dogs were given granulocyte colony-stimulating factor (G-CSF) after their initial transplantation to mobilize the cells. Despite successful allogeneic HCT and a permissive environment for donor muscle engraftment, there was no detectable contribution of bone marrow-derived cells to either skeletal muscle or muscle precursor cells assayed by clonal analyses at a level of sensitivity that should detect as little as 0.1% donor contribution.
杜兴氏肌营养不良症（DMD）是由X染色体上的肌营养不良蛋白基因突变引起的，该突变会导致骨骼肌和心肌损伤以及过早死亡。对小鼠的研究，包括DMD的mdx小鼠模型，已经证明循环骨髓来源的细胞可以参与骨骼肌再生，但通过健康供体的异体骨髓移植治疗人类DMD的潜在临床效用仍然未知。为了评估异体造血细胞移植（HCT）是否能为患有犬X连锁肌营养不良症（c-xmd）的犬提供临床上相关水平的供体肌肉细胞贡献，7只c-xmd犬接受了来自未受影响同窝仔犬的造血细胞（HC）移植。与移植前的基线相比，HCT后肌营养不良蛋白阳性纤维的数量和野生型肌营养不良蛋白RNA的量没有增加，观察期为28至417天。当受体犬在初次移植后给予粒细胞集落刺激因子（G-CSF）以动员细胞时，也获得了类似的结果。尽管异体HCT成功且存在允许供体肌肉植入的环境，但通过克隆分析检测，在灵敏度水平应能检测到低至0.1%的供体贡献的情况下，未检测到骨髓来源的细胞对骨骼肌或肌肉前体细胞有任何贡献。
