Gussoni E, Blau H M, Kunkel L M
Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
Nat Med. 1997 Sep;3(9):970-7. doi: 10.1038/nm0997-970.
Muscle biopsies from six patients with Duchenne muscular dystrophy (DMD) participating in a myoblast transplantation clinical trial were reexamined using a fluorescence in situ hybridization (FISH)-based method. Donor nuclei were detected in all biopsies analyzed, including nine where no donor myoblasts were previously thought to be present. In three patients, more than 10% of the original number of donor cells were calculated as present 6 months after implantation. Half of the detected donor nuclei were fused into host myofibers, and of these, nearly 50% produced dystrophin. These findings demonstrate that although donor myoblasts have persisted after injection, their microenvironment influences whether they fuse and express dystrophin. Our methodology could be used for developing new approaches to improve myoblast transfer efficacy and for the analysis of future gene- and/or cell-based therapies of numerous genetic disorders.
对参与成肌细胞移植临床试验的6例杜氏肌营养不良症（DMD）患者的肌肉活检样本，采用基于荧光原位杂交（FISH）的方法进行了重新检查。在所有分析的活检样本中均检测到了供体细胞核，其中包括9例之前认为不存在供体成肌细胞的样本。在3例患者中，植入6个月后计算得出的供体细胞数量超过了原始数量的10%。检测到的供体细胞核中有一半融合到了宿主肌纤维中，其中近50%产生了抗肌萎缩蛋白。这些发现表明，尽管供体成肌细胞在注射后持续存在，但其微环境会影响它们是否融合并表达抗肌萎缩蛋白。我们的方法可用于开发新方法以提高成肌细胞转移效率，并用于分析未来针对多种遗传疾病的基因和/或细胞疗法。
