Han Jongsoo, Lim Donghyun, Yang Kisuk
Department of Bioengineering and Nano-Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Republic of Korea.
Department of Bioengineering, College of Engineering, and BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, Republic of Korea.
J Tissue Eng. 2025 Sep 16;16:20417314251373039. doi: 10.1177/20417314251373039. eCollection 2025 Jan-Dec.
Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic β cells, leading to lifelong insulin dependence and significant health complications. Human pluripotent stem cell-derived β cells (hPSC-β cells) have emerged as a promising therapeutic alternative for restoring endogenous insulin production; however, limitations such as functional immaturity, immune rejection, and biosafety concerns such as tumorigenic risk continue to hinder clinical application. Recent advances in gene editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), offer precise tools to enhance or correct hPSC-β cell performance by improving glucose-stimulated insulin secretion (GSIS), reducing immune rejection, and reducing biosafety concerns. This review explores gene editing strategies developed to overcome the key barriers in hPSC-β cell-based therapy for T1D. We highlight how genetic modifications enhance or correct β cell function, promote immune evasion, and reduce biosafety concerns through precise and clinically relevant engineering. Finally, we discuss the current landscape of clinical trials and future directions for translating gene-edited hPSC-β cells into curative treatments for T1D.
1型糖尿病（T1D）是由胰腺β细胞的自身免疫性破坏引起的，导致终身依赖胰岛素并引发严重的健康并发症。人多能干细胞衍生的β细胞（hPSC-β细胞）已成为恢复内源性胰岛素分泌的一种有前景的治疗选择；然而，诸如功能不成熟、免疫排斥以及生物安全性问题（如致瘤风险）等限制因素仍然阻碍着其临床应用。基因编辑技术的最新进展，特别是成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关蛋白9（Cas9），提供了精确的工具，可通过改善葡萄糖刺激的胰岛素分泌（GSIS）、减少免疫排斥和降低生物安全性问题来增强或纠正hPSC-β细胞的性能。本综述探讨了为克服基于hPSC-β细胞治疗T1D的关键障碍而开发的基因编辑策略。我们强调了基因修饰如何通过精确且与临床相关的工程来增强或纠正β细胞功能、促进免疫逃逸并降低生物安全性问题。最后，我们讨论了将基因编辑的hPSC-β细胞转化为T1D治愈性治疗方法的临床试验现状和未来方向。
