Zhang Ke, Wang Yanqiu, An Qi, Ji Hengjing, Wu Defu, Li Xuri, Suo Lingge, Zhang Chun, Dong Xuran
Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Beijing, China.
Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Cell Prolif. 2025 May;58(5):e13785. doi: 10.1111/cpr.13785. Epub 2024 Dec 12.
Human induced pluripotent stem cells (hiPSCs) represent a promising cell source for generating functional cells suitable for clinical therapeutic applications, particularly in the context of autologous cell therapies. However, the production of hiPSCs through genetic manipulation, especially involving oncogenes, may raise safety concerns. Furthermore, the complexity and high costs associated with hiPSCs generation have hindered their broad clinical use. In this study, we utilised a recently developed chemical reprogramming method in conjunction with a guided differentiation protocol, introducing a chemically defined strategy for generating functional human retinal pigment epithelium (RPE) cells from adipose tissue, bypassing conventional hiPSCs generation challenges. By utilising small molecule-based chemical cocktails, we reprogrammed somatic adipose cells into human chemically induced pluripotent stem cells (hCiPSCs) in a safer and more streamlined manner, entirely free from gene manipulation. Subsequent differentiation of hCiPSCs into functional RPE cells demonstrated their capability for secretion and phagocytosis, emphasising their vital role in maintaining retinal homeostasis and underscoring their therapeutic potential. Our findings highlight the transformative potential of hCiPSCs as a safer, more efficient option for personalised cell therapies, with applications extending beyond ocular disease to a wide range of medical conditions.
人诱导多能干细胞（hiPSC）是一种很有前景的细胞来源，可用于生成适用于临床治疗应用的功能性细胞，尤其是在自体细胞治疗的背景下。然而，通过基因操作，特别是涉及致癌基因来生产hiPSC，可能会引发安全问题。此外，与hiPSC生成相关的复杂性和高成本阻碍了它们在临床上的广泛应用。在本研究中，我们利用了一种最近开发的化学重编程方法，并结合一种定向分化方案，引入了一种化学定义策略，从脂肪组织中生成功能性人视网膜色素上皮（RPE）细胞，绕过了传统hiPSC生成面临的挑战。通过使用基于小分子的化学混合物，我们以一种更安全、更简化的方式将体细胞脂肪细胞重编程为人化学诱导多能干细胞（hCiPSC），完全无需基因操作。随后将hCiPSC分化为功能性RPE细胞，证明了它们具有分泌和吞噬能力，突出了它们在维持视网膜稳态中的重要作用，并强调了它们的治疗潜力。我们的研究结果突出了hCiPSC作为个性化细胞治疗更安全、更有效选择的变革潜力，其应用范围不仅限于眼部疾病，还可扩展到广泛的医疗状况。
