Donders lnstitute for Brain Cognition and Behavior, Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, The Netherlands.
Donders lnstitute for Brain Cognition and Behavior, Department of Neurology, Radboud University Medical Center, 6525, GA, Nijmegen, The Netherlands.
Stem Cell Rev Rep. 2021 Jun;17(3):878-899. doi: 10.1007/s12015-020-10100-y. Epub 2020 Dec 21.
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.
骨骼肌的内在再生能力使其成为细胞治疗的理想目标。然而，在肌肉营养不良症 (MD) 中，肌肉组织的更新潜力通常已经耗尽且不足，MD 是一组具有不同遗传异质性的疾病，表现为骨骼肌纤维进行性丧失。MD 的细胞治疗必须依赖于补充具有高成肌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，重点是存在于骨骼肌中的成体干细胞和祖细胞。早期探索了成肌细胞和成肌卫星细胞的潜力，但令人失望的临床结果后，该领域转向了其他肌肉祖细胞，每种细胞都有其自身的优点和缺点。最近，中胚层成血管细胞和成纤维细胞被用于肌肉细胞治疗，从而进行了一些临床前研究和临床试验。目前最常见的 MD 形式的（前）临床工作的现状说明了存在的挑战和瓶颈。除了可移植细胞的内在特性外，我们还讨论了与细胞扩增和移植后细胞活力、最佳剂量以及给药途径和时间相关的问题。由于 MD 是遗传疾病，自体细胞治疗和基因治疗将需要携手合作，带来额外的并发症。最后，我们讨论了优化肌肉细胞治疗未来临床试验的决定因素。联合研究工作带来了希望，即针对 MD 的有效治疗方法即将出现，以满足患者未满足的临床需求。
