Schaaf Christopher, Sussel Lori
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Denver, Colorado, USA.
Diabetes Technol Ther. 2025 Jun;27(6):413-421. doi: 10.1089/dia.2024.0498. Epub 2025 Feb 6.
Type 1 diabetes (T1D) affects over 2 million people in the United States and has no known cure. The discovery and first use of insulin in humans 102 years ago marked a revolutionary course of treatment for the disease, and although the formulations and delivery systems have advanced, insulin administration remains the standard of care today. While improved treatment options represent notable progress in T1D management, finding a functional cure for the disease remains the ultimate goal. Approaches to curing T1D have historically focused on blunting the autoimmune response, although sustained effects of immune modulation have proven elusive. Islet transplant therapies have also proven effective, although a lack of available donor tissue and the need for immunosuppression to prevent both host-graft rejection and the autoimmune response have reserved such treatments for those who already require immunosuppressive regimens for other reasons or undergo severe hypoglycemic events in conjunction with hypoglycemic unawareness. With the advent of human stem cell research, the focus has shifted toward generating an abundance of allogeneic, functional beta-like cells that can be transplanted into the patients. Immunoisolation devices have also shown some promise as a method of preventing immune rejection and the autoimmune destruction of transplanted cells. Finally, advances in new immune therapies, if used in the early stages of T1D progression, have proven to delay the onset of diabetes. Stem cell-based therapies are a promising approach to curing T1D. The ongoing clinical trials show some success, although they currently require immunosuppressant agents. Encapsulation devices provide a method of immunoisolation that does not require immunosuppression; however, the devices tested thus far eventually lead to cell death and fibrotic tissue growth. Substantial research efforts are underway to develop new approaches to protect the stem cell-derived beta cells upon transplantation.
1型糖尿病（T1D）在美国影响着超过200万人，目前尚无治愈方法。102年前胰岛素在人体中的发现和首次使用标志着该疾病治疗的革命性进程，尽管制剂和给药系统已经取得了进展，但胰岛素给药仍是当今的标准治疗方法。虽然改进的治疗方案在T1D管理方面取得了显著进展，但找到该疾病的功能性治愈方法仍然是最终目标。治疗T1D的方法历来侧重于抑制自身免疫反应，尽管免疫调节的持续效果难以实现。胰岛移植疗法也已被证明是有效的，尽管缺乏可用的供体组织以及需要免疫抑制来防止宿主移植物排斥和自身免疫反应，使得这种治疗仅适用于那些因其他原因已经需要免疫抑制方案或同时经历严重低血糖事件且伴有低血糖无知觉的患者。随着人类干细胞研究的出现，重点已转向生成大量可移植到患者体内的同种异体、功能性β样细胞。免疫隔离装置作为一种防止免疫排斥和移植细胞自身免疫破坏的方法也显示出了一些前景。最后，新的免疫疗法如果在T1D进展的早期阶段使用，已被证明可以延缓糖尿病的发作。基于干细胞的疗法是治愈T1D的一种有前途的方法。正在进行的临床试验显示出了一些成功，尽管目前它们需要免疫抑制剂。封装装置提供了一种无需免疫抑制的免疫隔离方法；然而，迄今为止测试的装置最终会导致细胞死亡和纤维化组织生长。目前正在进行大量研究工作，以开发新的方法来在移植后保护干细胞衍生的β细胞。
