Chemical and Biological Engineering, Koc University, Sariyer, 34450, Istanbul, Turkey.
Department of Chemistry, CICECO - Aveiro Institute of Materials. University of Aveiro. Campus Universitário de Santiago. 3810-193 Aveiro. Portugal.
Biomaterials. 2021 Feb;269:120627. doi: 10.1016/j.biomaterials.2020.120627. Epub 2020 Dec 21.
Islet transplantation has proved one of the most remarkable transmissions from an experimental curiosity into a routine clinical application for the treatment of type I diabetes (T1D). Current efforts for taking this technology one-step further are now focusing on overcoming islet donor shortage, engraftment, prolonged islet availability, post-transplant vascularization, and coming up with new strategies to eliminate lifelong immunosuppression. To this end, insulin secreting 3D cell clusters composed of different types of cells, also referred as heterocellular islet organoids, spheroids, or pseudoislets, have been engineered to overcome the challenges encountered by the current islet transplantation protocols. β-cells or native islets are accompanied by helper cells, also referred to as accessory cells, to generate a cell cluster that is not only able to accurately secrete insulin in response to glucose, but also superior in terms of other key features (e.g. maintaining a vasculature, longer durability in vivo and not necessitating immunosuppression after transplantation). Over the past decade, numerous 3D cell culture techniques have been integrated to create an engineered heterocellular islet organoid that addresses current obstacles. Here, we first discuss the different cell types used to prepare heterocellular organoids for islet transplantation and their contribution to the organoids design. We then introduce various cell culture techniques that are incorporated to prepare a fully functional and insulin secreting organoids with select features. Finally, we discuss the challenges and present a future outlook for improving clinical outcomes of islet transplantation.
胰岛移植已被证明是将实验好奇心转化为治疗 1 型糖尿病 (T1D) 的常规临床应用的最显著进展之一。目前，进一步推进这项技术的努力集中在克服胰岛供体短缺、移植、延长胰岛可用性、移植后血管化以及提出新策略以消除终身免疫抑制。为此，由不同类型细胞组成的具有胰岛素分泌功能的 3D 细胞簇，也称为异细胞胰岛类器官、球体或假胰岛，已被工程化用于克服当前胰岛移植方案所面临的挑战。β细胞或天然胰岛伴随着辅助细胞，也称为辅助细胞，以产生不仅能够准确地响应葡萄糖分泌胰岛素的细胞簇，而且在其他关键特性方面更优越（例如维持血管、在体内具有更长的耐久性并且在移植后不需要免疫抑制）。在过去的十年中，已经整合了许多 3D 细胞培养技术来创建一个工程化的异细胞胰岛类器官，以解决当前的障碍。在这里，我们首先讨论用于胰岛移植的异细胞类器官制备中使用的不同细胞类型及其对类器官设计的贡献。然后，我们介绍了各种细胞培养技术，这些技术被整合到制备具有特定功能和胰岛素分泌功能的完全功能性类器官中。最后，我们讨论了挑战，并对改善胰岛移植的临床结果提出了未来展望。
