Fonseca Laura Mar, Krause Nicerine, Lebreton Fanny, Berishvili Ekaterine
Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery, University of Geneva, Geneva, Switzerland.
Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Artif Organs. 2025 Apr;49(4):541-555. doi: 10.1111/aor.14950. Epub 2025 Jan 23.
Intrahepatic islet transplantation is a promising strategy for β-cell replacement therapy in the treatment of Type 1 Diabetes. However, several obstacles hinder the long-term efficacy of this therapy. A major challenge is the scarcity of donor organs. During the isolation process, islets are disconnected from their extracellular matrix (ECM) and vasculature, leading to significant loss due to anoikis and hypoxia. Additionally, inflammatory and rejection reactions further compromise islet survival and engraftment success. Extensive efforts are being made to improve the efficacy of islet transplantation. These strategies include promoting revascularization and ECM support through bioengineering techniques, exploring alternative sources of insulin-secreting cells, and providing immunomodulation for the graft. Despite these advancements, a significant gap remains in integrating these strategies into a cohesive approach that effectively replicates the native endocrine environment. Specifically, the lack of comprehensive methods to address both the structural and functional aspects of the endocrine niche limits reproducibility and clinical translation. Therefore, bioengineering an endocrine pancreas must aim to recreate the endocrine niche to achieve lifelong efficacy and insulin independence. This review discusses various strategies developed to produce the building blocks for generating a vascularized, immune-protected insulin-secreting construct, emphasizing the importance of the endocrine niche's composition and function.
肝内胰岛移植是1型糖尿病β细胞替代治疗的一种有前景的策略。然而，有几个障碍阻碍了这种治疗的长期疗效。一个主要挑战是供体器官的稀缺。在分离过程中，胰岛与细胞外基质（ECM）和脉管系统分离，导致由于失巢凋亡和缺氧而造成大量损失。此外，炎症和排斥反应进一步损害胰岛存活和移植成功率。人们正在做出广泛努力来提高胰岛移植的疗效。这些策略包括通过生物工程技术促进血管再生和ECM支持、探索胰岛素分泌细胞的替代来源以及为移植物提供免疫调节。尽管有这些进展，但在将这些策略整合为一种有效复制天然内分泌环境的连贯方法方面仍存在重大差距。具体而言，缺乏解决内分泌微环境结构和功能方面的综合方法限制了可重复性和临床转化。因此，生物工程化内分泌胰腺必须旨在重建内分泌微环境，以实现终身疗效和胰岛素自主。本综述讨论了为生成血管化、免疫保护的胰岛素分泌构建体的组成部分而开发的各种策略，强调了内分泌微环境组成和功能的重要性。
