编辑丨王多鱼 排版丨水成文 糖尿病的细胞治疗 长期受限于一个 悬而未决 的根本难题—— 移植后的 胰岛 β 细胞难以在糖尿病病理 微 环境中实现长期存活并维持稳定功能 。临床随访数据表 明，多数胰岛移植在约 5 年后出现显著的 β 细胞功能衰退与治疗效果减弱。 干细胞来源的 β 细胞 （SC- β细胞 ） 也面临相同的困境。 这一移植后的" 长期 存活瓶颈"，已成为制约糖尿病细胞治疗进一步走向临床应用与规模化推广的关 键因素。如何突破该瓶颈，实现具备长期稳定疗效、甚至"一次性"治愈潜力的治疗方案，正是当前糖尿病细胞治疗领域亟需解决的核心目标。 该研究揭示了在糖尿病发生发展过程中， 锌离子异常积累 是导致 β 细胞身份丢失的核心驱动因素 ， 并 证实介导 锌离子积累 的转运蛋白 Z nT8 是 糖尿病预防 与治疗 的重要靶点。该研究发现， β 细胞内 过载的锌 持续 激活整合应激反应 （ ISR） ， 并 通过 ISR 下游转录因子 ATF4 启动 α 细胞特异性转录因子 ARX 异位 表达，从而在分子层面推动 β 细胞转分化。 这一发现为糖尿病细胞治疗长期疗效不足提供了全新解释与潜在干预靶点。 基于上述机制， ...

Core Viewpoint - The research on pluripotent stem cell-derived islets (PSC-islets) shows promising potential for treating diabetes by restoring blood glucose control through the transplantation of functional insulin-producing β cells [2][4]. Group 1: Research Findings - A study published in September 2024 demonstrated successful treatment of a type 1 diabetes patient using chemically reprogrammed pluripotent stem cell-derived islets (CiPSC-islets), resulting in the patient no longer needing external insulin therapy after one year [2]. - The research published in August 2025 established a method to generate islets with complete endocrine cell types from human pluripotent stem cells (iPSCs), which effectively respond to blood glucose changes and provide hypoglycemia protection in diabetic mouse models [3][4]. - The newly constructed PSC-islets contain all five endocrine cell types (α, β, δ, ε, and γ), showcasing a robust protective effect against hypoglycemia, with only 3% of measurements falling below 54 mg/dL compared to 59% in the control group [4][10]. Group 2: Implications for Diabetes Treatment - The study highlights a strategy for controlling the relative abundance of endocrine subtypes in PSC-islets, laying the groundwork for calibrating blood glucose homeostasis and providing clear hypoglycemia protection post-transplantation [6]. - The engineered islet cell composition replicates the dual blood glucose regulation function of natural islets, which is crucial for achieving precise blood glucose control and minimizing hypoglycemia risks [8]. - This advancement offers further safety assurance for the clinical translation of stem cell-derived islets, potentially accelerating the clinical application of diabetes cell therapies [8].