Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 119334 Moscow, Russia.
Department of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Biomolecules. 2022 Jun 9;12(6):810. doi: 10.3390/biom12060810.
Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion-one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems.
时至今日，1 型糖尿病（T1D）和 2 型糖尿病（T2D）的治疗已经取得了巨大的进展。然而，基于胰岛素注射和尸体胰岛移植的现代糖尿病治疗方法有许多缺点。这就是为什么研究人员正在开发新的方法来体外再生产生胰腺激素的细胞。最有前途的方法是生成由干细胞衍生而来的β细胞，从而为胰岛素分泌细胞提供无限的来源。最近的研究提供了产生β样细胞簇的方法，这些细胞簇显示出葡萄糖刺激的胰岛素分泌——β细胞的关键特征之一。然而，与天然β细胞相比，干细胞衍生的β细胞不会经历完全的功能成熟。在本文中，我们回顾了各种方案的发展和现状，考虑了它们的优点，并提出了改进它们的方法。我们研究了分子途径、表观遗传修饰、细胞内成分和微环境作为促进β细胞功能成熟的可能手段。还研究了从干细胞衍生成分创建胰岛类器官及其封装和进一步移植的可能性。我们试图将β细胞及其相互作用的现代研究结合起来，以创建一个关于开发胰岛素分泌系统的整体概述。
