人诱导多能干细胞来源细胞治疗产品的临床前安全性评价研究进展

Progress in preclinical safety evaluation of cell products derived from human induced pluripotent stem cells

干细胞作为再生医学的重要手段与研究核心,在临床重大难治性疾病治疗方面显现出巨大的应用价值。其中,诱导多能干细胞因其供体细胞限制少、质量稳定、伦理限制较少等优势,应用越来越广泛。尤其是多能干细胞定向分化技术和基因编辑技术等的逐步成熟,极大地加速了诱导多能干细胞衍生细胞疗法的发展。由诱导多能干细胞衍生分化的细胞治疗产品在非临床研究中证实了有效性和安全性,但诱导多能干细胞是通过人体来源的终端体细胞重编程而来,其衍生细胞产品的生产工艺与质量控制极为复杂,此类细胞产品应用到临床,仍然可能存在较大的安全性风险,例如成瘤性、异位分布、免疫排斥等潜在的风险。文章将介绍诱导多能干细胞及衍生细胞产品的基本概念和特点,并以治疗帕金森疾病的干细胞产品为例,着重探讨在非临床研究阶段可能存在的问题及采取的评价策略。

As an important means and research core of regenerative medicine,stem cells have shown great application value in the treatment of major clinical refractory diseases.Among them,induced pluripotent stem cells(iPSC)are more and more widely used because of their advantages such as less restriction of donor cells,stable quality and less ethical restrictions.In particular,the gradual maturation of pluripotent stem cell directed differentiation technology and gene editing technology has greatly accelerated the development of iPSC-derived cell therapy.The efficacy and safety of cell therapy products derived from induced pluripotent stem cells have been confirmed in non-clinical studies.However,iPSC are derived from the reprogramming of terminal somatic cells from human sources,and the production process and quality control of its derived cell products are extremely complicated.Therefore,there may still be large safety risks in the clinical application of such cell products,such as,tumorigenicity,ectopic distribution,immune rejection and other potential risks.This paper will introduce the basic concepts and characteristics of iPSC and their derived cell products,