Institute of Cytology, Russian Academy of Sciences, 194064 Saint-Petersburg, Russia.
Int J Mol Sci. 2023 May 17;24(10):8892. doi: 10.3390/ijms24108892.
Duchenne muscular dystrophy (DMD) is a severe muscular disorder caused by mutations in the dystrophin gene. It leads to respiratory and cardiac failure and premature death at a young age. Although recent studies have greatly deepened the understanding of the primary and secondary pathogenetic mechanisms of DMD, an effective treatment remains elusive. In recent decades, stem cells have emerged as a novel therapeutic product for a variety of diseases. In this study, we investigated nonmyeloablative bone marrow cell (BMC) transplantation as a method of cell therapy for DMD in an mdx mouse model. By using BMC transplantation from GFP-positive mice, we confirmed that BMCs participate in the muscle restoration of mdx mice. We analyzed both syngeneic and allogeneic BMC transplantation under different conditions. Our data indicated that 3 Gy X-ray irradiation with subsequent BMC transplantation improved dystrophin synthesis and the structure of striated muscle fibers (SMFs) in mdx mice as well as decreasing the death rate of SMFs. In addition, we observed the normalization of neuromuscular junctions (NMJs) in mdx mice after nonmyeloablative BMC transplantation. In conclusion, we demonstrated that nonmyeloablative BMC transplantation could be considered a method for DMD treatment.
杜氏肌营养不良症（DMD）是一种严重的肌肉疾病，由 dystrophin 基因突变引起。它会导致呼吸和心脏衰竭，并在年轻时导致过早死亡。尽管最近的研究极大地加深了对 DMD 的主要和次要发病机制的理解，但仍缺乏有效的治疗方法。近几十年来，干细胞已成为治疗多种疾病的一种新型治疗产品。在这项研究中，我们研究了非清髓性骨髓细胞（BMC）移植作为 mdx 小鼠模型中 DMD 的细胞治疗方法。通过使用 GFP 阳性小鼠的 BMC 移植，我们证实 BMC 参与了 mdx 小鼠的肌肉修复。我们分析了不同条件下的同基因和同种异体 BMC 移植。我们的数据表明，3Gy X 射线照射后进行 BMC 移植可改善 mdx 小鼠的肌营养不良蛋白合成和横纹肌纤维（SMF）结构，并降低 SMF 的死亡率。此外，我们观察到非清髓性 BMC 移植后 mdx 小鼠的神经肌肉接头（NMJ）正常化。总之，我们证明了非清髓性 BMC 移植可以被认为是一种治疗 DMD 的方法。
