Tominari Tsukasa, Sathyaprakash Chaitra, Aoki Yoshitsugu
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Front Cell Dev Biol. 2025 Sep 3;13:1640275. doi: 10.3389/fcell.2025.1640275. eCollection 2025.
Duchenne muscular dystrophy is a genetic disease where loss of sarcolemma-associated protein, dystrophin, leads to progressive muscle wasting, and eventual loss of life from complications linked to cardiac deficits. Currently, numerous molecular therapies to restore dystrophin have entered clinical trials. However, the therapeutic benefits of these strategies in promoting tissue regeneration and reducing fibrosis remain limited. Stem/progenitor cell-based therapy in DMD patients is a promising strategy to promote muscle regeneration, though the conditions of transplantation and pre-treatments of numerous cell types are still being optimized. Several cell types with different properties and origins, such as myogenic stem/progenitor cells, mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs), have been studied for treating DMD. Myogenic stem/progenitor cells derived from healthy donors are expected to restore the number of myofibers as well as dystrophin expression in DMD muscles. MSCs derived from various tissues, including umbilical cord, have immunosuppressive properties and are expected to ameliorate DMD phenotypes in combination with other gene therapies. In this review, we will summarize the challenges that must be overcome to allow for successful DMD muscle tissue regeneration and review the latest findings in stem/progenitor cell-based DMD therapy. We will focus on the pre-conditioning of cells for replacement therapies and treatment of the disease niche to improve muscle fiber integration.
杜氏肌营养不良症是一种遗传性疾病,其中肌膜相关蛋白肌营养不良蛋白的缺失会导致进行性肌肉萎缩,并最终因与心脏缺陷相关的并发症而失去生命。目前,许多恢复肌营养不良蛋白的分子疗法已进入临床试验。然而,这些策略在促进组织再生和减少纤维化方面的治疗益处仍然有限。在杜氏肌营养不良症患者中基于干细胞/祖细胞的疗法是促进肌肉再生的一种有前景的策略,尽管多种细胞类型的移植条件和预处理仍在优化中。几种具有不同特性和来源的细胞类型,如成肌干细胞/祖细胞、间充质干细胞(MSCs)和诱导多能干细胞(iPSCs),已被研究用于治疗杜氏肌营养不良症。来自健康供体的成肌干细胞/祖细胞有望恢复杜氏肌营养不良症肌肉中的肌纤维数量以及肌营养不良蛋白的表达。来自包括脐带在内的各种组织的间充质干细胞具有免疫抑制特性,有望与其他基因疗法联合改善杜氏肌营养不良症的表型。在这篇综述中,我们将总结为实现成功的杜氏肌营养不良症肌肉组织再生必须克服的挑战,并回顾基于干细胞/祖细胞的杜氏肌营养不良症治疗的最新发现。我们将重点关注用于替代疗法的细胞预处理以及疾病微环境的治疗,以改善肌纤维整合。