Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation
Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation
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DOI：
10.1172/jci200216098
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发表时间：
2002-09-01
影响因子：
15.9
通讯作者：
Weinberg, K
中科院分区：
文献类型：
--
作者：
Gussoni, E;Bennett, RR;Weinberg, K
杜氏肌营养不良症 (DMD) 是一种由肌营养不良蛋白基因突变引起的严重进行性肌肉萎缩性疾病。研究表明，将骨髓细胞移植到接受致命辐射的 mdx 小鼠（DMD 小鼠模型）中，可以成为骨骼肌肌纤维的一部分。人类骨髓细胞是否也具有这种能力尚不清楚。在此，我们报告对一名 DMD 患者 (DMD-BMT1) 的肌肉活检分析，该患者在 1 岁时因 X 连锁严重联合免疫缺陷接受骨髓移植，并在 12 岁时被诊断患有 DMD。对 DMD-BMT1 肌肉活检的分析显示，少量肌肉肌纤维 (0.5-0.9%) 中存在供体核。大多数肌纤维产生缺乏外显子 44 和 45 的截短的框内亚型抗肌萎缩蛋白（非野生型）。该患者肌肉中存在骨髓来源的供体细胞核，这证明了外源人骨髓细胞能够融合到骨骼肌中，并在移植后持续存在长达 13 年。
Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder caused by mutations in the dystrophin gene. Studies have shown that bone marrow cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can become part of skeletal muscle myofibers. Whether human marrow cells also have this ability is unknown. Here we report the analysis of muscle biopsies from a DMD patient (DMD-BMT1) who received bone marrow transplantation at age 1 year for X-linked severe combined immune deficiency and who was diagnosed with DMD at age 12 years. Analysis of muscle biopsies from DMD-BMT1 revealed the presence of donor nuclei within a small number of muscle myofibers (0.5-0.9%). The majority of the myofibers produce a truncated, in-frame isoform of dystrophin lacking exons 44 and 45 (not wild-type). The presence of bone marrow-derived donor nuclei in the muscle of this patient documents the ability of exogenous human bone marrow cells to fuse into skeletal muscle and persist up to 13 years after transplantation.