Lemos Joana R N, Skyler Jay S
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Horm Res Paediatr. 2024 Oct 30:1-15. doi: 10.1159/000542206.
Type 1 diabetes (T1D), a disease characterized by immune-mediated destruction of beta-cells, presents a significant global health challenge. Achieving therapeutic goals such as prevention of immune destruction, preservation of beta-cell mass, and automated insulin delivery remains complex due to the disease's heterogeneity.
This review explores the advancements and challenges in beta-cell replacement therapies, including pancreas and islet cell transplantation, stem cell-derived β-cell generation, and biotechnological innovations. Pancreas transplantation, especially simultaneous pancreas and kidney transplantation, has evolved significantly, offering insulin independence and improved quality of life despite surgical and immunological complications. Allogeneic islet transplantation, though less invasive, faces challenges such as donor scarcity, immunosuppressive therapy, and variable long-term success. Innovations in stem cell therapy, particularly using human embryonic stem cells and induced pluripotent stem cells, promise an unlimited source of β-cells. However, translating these advances into clinical applications involves overcoming technical, biological, and ethical hurdles. Strategies such as immunomodulation, encapsulation, and genetic engineering are critical to enhancing the viability and integration of transplanted cells.
This review provides a comprehensive overview of the scientific intricacies and potential of β-cell replacement therapies, emphasizing the need for continued research to address the remaining challenges and improve diabetes care outcomes.
1型糖尿病(T1D)是一种以β细胞免疫介导性破坏为特征的疾病,对全球健康构成重大挑战。由于该疾病的异质性,实现诸如预防免疫破坏、保留β细胞量以及自动胰岛素输送等治疗目标仍然很复杂。
本综述探讨了β细胞替代疗法的进展和挑战,包括胰腺和胰岛细胞移植、干细胞衍生β细胞的生成以及生物技术创新。胰腺移植,尤其是胰肾联合移植,已经有了显著发展,尽管存在手术和免疫并发症,但能实现胰岛素自主并改善生活质量。同种异体胰岛移植虽然侵入性较小,但面临供体短缺、免疫抑制治疗以及长期成功率不一等挑战。干细胞疗法的创新,特别是使用人类胚胎干细胞和诱导多能干细胞,有望提供无限的β细胞来源。然而,将这些进展转化为临床应用需要克服技术、生物学和伦理障碍。免疫调节、封装和基因工程等策略对于提高移植细胞的存活率和整合至关重要。
本综述全面概述了β细胞替代疗法的科学复杂性和潜力,强调需要持续研究以应对剩余挑战并改善糖尿病护理结果。