PDF(Pubmed)
Abstract：
Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs\' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.
摘要：
诱导多能干细胞（iPSCs）衍生的细胞疗法由于iPSCs的可扩展性，在再生医学领域提供了一个有希望的途径，免疫相容性，和多能潜能。开展了越来越多的临床前和临床试验,探索基于iPSC的疗法在挑战性疾病中的应用，如肌肉营养不良。骨骼肌独特的合胞体性质允许干/祖细胞整合，形成新的肌核并恢复受肌病影响的基因的表达。这一特征使得基因组编辑技术在这些疗法中特别有吸引力。使用遗传修饰和iPSC谱系规范方法，可以制造免疫相容的健康iPSC衍生的肌肉细胞以逆转肌肉疾病的进展或促进组织再生。尽管取得了令人兴奋的进步，基于iPSC的肌肉疾病和组织再生疗法的大部分发展仅限于学术环境，没有成功的临床翻译报告。体内未知的分化过程，潜在的致瘤性，移植细胞的表观遗传异常阻碍了其临床应用。在这次审查中,我们概述了iPSC衍生的肌原细胞移植疗法的临床前发展，包括与iPSC衍生的肌原细胞相关的过程，如分化，放大，delivery,和cGMP合规性。我们讨论了临床翻译每个步骤的潜在挑战。此外,描述了用于临床应用的用于测试肌原细胞的临床前模型系统。
