Bose Devika, Ortolan Davide, Farnoodian Mitra, Sharma Ruchi, Bharti Kapil
Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Cold Spring Harb Perspect Med. 2024 Mar 1;14(3):a041295. doi: 10.1101/cshperspect.a041295.
Cell-replacement therapies are a new class of treatments, which include induced pluripotent stem cell (iPSC)-derived tissues that aim to replace degenerated cells. iPSCs can potentially be used to generate any cell type of the body, making them a powerful tool for treating degenerative diseases. Cell replacement for retinal degenerative diseases is at the forefront of cell therapies, given the accessibility of the eye for surgical procedures and a huge unmet medical need for retinal degenerative diseases with no current treatment options. Clinical trials are ongoing in different parts of the world using stem cell-derived retinal pigment epithelium (RPE). This review focuses on scientific and regulatory considerations when developing an iPSC-derived RPE cell therapy from the development of a robust and efficient differentiation protocol to critical quality control assays for cell validation, the choice of an appropriate animal model for preclinical testing, and the regulatory aspects that dictate the final approval for proceeding to a first-in-human clinical trial.
细胞替代疗法是一类新型治疗方法，其中包括诱导多能干细胞（iPSC）衍生的组织，旨在替代退化细胞。iPSC有潜力用于生成身体的任何细胞类型，使其成为治疗退行性疾病的有力工具。鉴于眼睛便于进行外科手术，且视网膜退行性疾病存在巨大的未满足医疗需求且目前没有治疗选择，视网膜退行性疾病的细胞替代疗法处于细胞治疗的前沿。世界各地正在进行使用干细胞衍生的视网膜色素上皮（RPE）的临床试验。本综述重点关注从开发强大且高效的分化方案到细胞验证的关键质量控制检测、选择合适的动物模型进行临床前测试以及决定首次人体临床试验最终批准的监管方面等，开发iPSC衍生的RPE细胞疗法时的科学和监管考量。
