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SDG框架在iPSC细胞治疗质量控制与临床转化中的应用前景. (2026). 环球医学研究, 3(4), 145-153. https://doi.org/10.62836/medicine.v3i4.1430
Copyright (c) 2026 梁睿妹, 孟东, 张月园, 李忠, 白宗科
This work is licensed under a Creative Commons Attribution 4.0 International License.
SDG框架在iPSC细胞治疗质量控制与临床转化中的应用前景
梁睿妹1，孟东2，张月园1，李忠3*，白宗科2,3*
1. 药物研发中心，深圳泽医细胞治疗集团，深圳
2. 深圳泽医医院，深圳泽医细胞治疗集团，深圳
3. 细胞治疗研究院，深圳泽医细胞治疗集团，深圳
摘要：诱导成熟细胞成为多能干细胞的技术，即诱导多功能干细胞（Induced pluripotent stem cell, iPSC），已经成为疾病建模、药物筛选和个性化细胞治疗的重要工具。iPSC本身处于未成熟，或“胎儿样”或“社会幼稚”状态。当移植到成熟组织或体外组织分化成熟模型中，iPSC需要通过与移植环境相互作用，逐渐分化成熟。我们称之为“社会化依赖性生长”（Socialization-dependent growth，SDG），所以细胞社会化（Cell socialization)成为iPSC在多细胞环境中生长要面临的首要问题。iPSC需要通过细胞接触、旁分泌信号、物理微环境和代谢调节，获得代谢适应、组织分化、通讯响应和环境感知的四维能力，最终成为细胞应用产品，SDG实际上贯穿了重编程、谱系分化、微环境塑造及移植后宿主响应的连续机制链，在多细胞组织化环境中，助力iPSC通过适应和改变电生理、代谢、突触和组织结构，实现社会化成熟。因此，本文围绕iPSC衍生细胞功能成熟这一关键瓶颈，提出SDG概念框架，系统总结细胞互作、微环境调控及宿主整合对细胞成熟的影响，并探讨其在细胞治疗产品质量控制和临床转化中的潜在价值。
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[4] Funakoshi S., Yoshida Y. Recent progress of iPSC technology in cardiac diseases [J]. Arch Toxicol, 2021, 95(12): 3633-50.
[5] Shahannaz D.C., Sugiura T., Ferrell B.E., et al. Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives [J]. Medicina (Kaunas), 2025, 61(11): 2056.
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[7] Corbett J.L., Duncan S.A. iPSC-Derived Hepatocytes as a Platform for Disease Modeling and Drug Discovery [J]. Front Med (Lausanne), 2019, 6: 265.
[8] Luo Q., Wang N., Que H., et al. Pluripotent Stem Cell-Derived Hepatocyte-like Cells: Induction Methods and Applications [J]. Int J Mol Sci, 2023, 24(14): 11592.
[9] Mertens J., Reid D., Lau S., et al. Aging in a Dish: iPSC-Derived and Directly Induced Neurons for Studying Brain Aging and Age-Related Neurodegenerative Diseases [J]. Annu Rev Genet, 2018, 52: 271-93.
[10] Ciceri G., Baggiolini A., Cho H.S., et al. An epigenetic barrier sets the timing of human neuronal maturation [J]. Nature, 2024, 626(8000): 881-90.
[11] Hergenreder E., Minotti A.P., Zorina Y., et al. Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons [J]. Nat Biotechnol, 2024, 42(10): 1515-25.
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[18] Scuderi S., Kang T.Y., Jourdon A., et al. Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines [J]. Cell Stem Cell, 2025, 32(6): 970-89 e11.
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[22] Takebe T., Sekine K., Enomura M., et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant [J]. Nature, 2013, 499(7459): 481-4.
[23] Lendemeijer B., Unkel M., Smeenk H., et al. Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes [J]. eNeuro, 2024, 11(9): ENEURO.0148-24.2024.
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[27] Silva A.C., Matthys O.B., Joy D.A., et al. Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids [J]. Cell Stem Cell, 2021, 28(12): 2137-52 e6.
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