Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland.
Transpl Int. 2020 Dec;33(12):1577-1588. doi: 10.1111/tri.13721. Epub 2020 Sep 27.
Diabetes is a major health issue of increasing prevalence. ß-cell replacement, by pancreas or islet transplantation, is the only long-term curative option for patients with insulin-dependent diabetes. Despite good functional results, pancreas transplantation remains a major surgery with potentially severe complications. Islet transplantation is a minimally invasive alternative that can widen the indications in view of its lower morbidity. However, the islet isolation procedure disrupts their vasculature and connection to the surrounding extracellular matrix, exposing them to ischemia and anoikis. Implanted islets are also the target of innate and adaptive immune attacks, thus preventing robust engraftment and prolonged full function. Generation of organoids, defined as functional 3D structures assembled with cell types from different sources, is a strategy increasingly used in regenerative medicine for tissue replacement or repair, in a variety of inflammatory or degenerative disorders. Applied to ß-cell replacement, it offers the possibility to control the size and composition of islet-like structures (pseudo-islets), and to include cells with anti-inflammatory or immunomodulatory properties. In this review, we will present approaches to generate islet cell organoids and discuss how these strategies can be applied to the generation of a bioartificial pancreas for the treatment of type 1 diabetes.
糖尿病是一种日益流行的主要健康问题。β细胞替代，通过胰腺或胰岛移植，是胰岛素依赖型糖尿病患者的唯一长期治愈选择。尽管功能结果良好，但胰腺移植仍然是一种主要的手术，具有潜在的严重并发症。胰岛移植是一种微创替代方法，由于其发病率较低，可以扩大适应证。然而，胰岛分离过程会破坏其血管系统和与周围细胞外基质的连接，使它们容易发生缺血和失巢凋亡。植入的胰岛也会成为先天和适应性免疫攻击的目标，从而阻止其强大的植入和长期完全功能。类器官的产生，被定义为用不同来源的细胞类型组装的功能性 3D 结构，是再生医学中用于组织替代或修复的一种策略，适用于多种炎症或退行性疾病。将其应用于β细胞替代，它提供了控制胰岛样结构（假胰岛）大小和组成的可能性，并可以包括具有抗炎或免疫调节特性的细胞。在这篇综述中，我们将介绍生成胰岛细胞类器官的方法，并讨论这些策略如何应用于生成用于治疗 1 型糖尿病的生物人工胰腺。
