The intrinsic regenerative capacity of skeletal muscle makes it an excellent target for cell therapy. However, the potential of muscle tissue to renew is typically exhausted and insufficient in muscular dystrophies (MDs), a large group of heterogeneous genetic disorders showing progressive loss of skeletal muscle fibers. Cell therapy for MDs has to rely on suppletion with donor cells with high myogenic regenerative capacity. Here, we provide an overview on stem cell lineages employed for strategies in MDs, with a focus on adult stem cells and progenitor cells resident in skeletal muscle. In the early days, the potential of myoblasts and satellite cells was explored, but after disappointing clinical results the field moved to other muscle progenitor cells, each with its own advantages and disadvantages. Most recently, mesoangioblasts and pericytes have been pursued for muscle cell therapy, leading to a handful of preclinical studies and a clinical trial. The current status of (pre)clinical work for the most common forms of MD illustrates the existing challenges and bottlenecks. Besides the intrinsic properties of transplantable cells, we discuss issues relating to cell expansion and cell viability after transplantation, optimal dosage, and route and timing of administration. Since MDs are genetic conditions, autologous cell therapy and gene therapy will need to go hand-in-hand, bringing in additional complications. Finally, we discuss determinants for optimization of future clinical trials for muscle cell therapy. Joined research efforts bring hope that effective therapies for MDs are on the horizon to fulfil the unmet clinical need in patients.

Graphical abstract

中文翻译：

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肌肉萎缩症的全身细胞疗法

骨骼肌的内在再生能力使其成为细胞治疗的绝佳靶点。然而，肌肉组织更新的潜力通常在肌营养不良症 (MDs) 中耗尽且不足，这是一大群异质性遗传疾病，表现出骨骼肌纤维的进行性丧失。MDs 的细胞疗法必须依赖于补充具有高肌源性再生能力的供体细胞。在这里，我们概述了用于 MD 策略的干细胞谱系，重点关注骨骼肌中的成体干细胞和祖细胞。早期，人们探索了成肌细胞和卫星细胞的潜力，但在令人失望的临床结果之后，该领域转向了其他肌肉祖细胞，它们各有优缺点。最近，中成血管细胞和周细胞已被用于肌肉细胞治疗，导致了一些临床前研究和临床试验。最常见的 MD 形式的（前）临床工作的现状说明了现有的挑战和瓶颈。除了可移植细胞的内在特性外，我们还讨论了与移植后细胞扩增和细胞活力、最佳剂量以及给药途径和时机有关的问题。由于 MD 是遗传病，自体细胞疗法和基因疗法需要齐头并进，带来额外的并发症。最后，我们讨论了优化未来肌肉细胞治疗临床试验的决定因素。联合研究工作带来了希望，即针对 MD 的有效疗法即将出现，以满足患者未满足的临床需求。

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