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面向国家重大需求　开发建立新研究模型——胰岛类器官模型的研究进展与展望

宋婀莉^*, 王璞玥

国家自然科学基金委员会生命科学部，北京 100085

摘要

糖尿病是威胁人类健康的一种重大代谢性疾病，给人们和社会带来了沉重的负担，对其发病机制的研究和治疗方法的开发是国家的重大需求。随着类器官技术的问世，胰岛类器官(islet organoid)应运而生且备受关注，被认为是极具价值的新型糖尿病研究模型。胰岛类器官是基于目前对胰岛发育机制的理解，通过体外添加诱导因子程序化地激活或抑制发育过程中的特定信号通路，将干细胞体外诱导分化成具有类似天然胰岛结构和功能的三维细胞培养物。由于胰岛类器官能够在一定程度上体外模拟胰岛的发育过程，体现其组织结构，行使分泌多种激素、调控血糖水平的生理功能，因此具有广泛的应用价值，已被用于糖尿病发病机制研究、药物筛选和评价以及临床移植治疗等，显示出良好的应用前景。本文主要总结和介绍胰岛类器官目前的研究进展、应用前景和亟待解决的问题，并且讨论和展望未来的发展方向。

关键词： 类器官; 胰岛类器官; 糖尿病; 研究模型; 研究进展

Focusing on the major national demands and developing novel research models——the research progress and prospective of islet organoid

SONG E-Li^*, WANG Pu-Yue

Department of Life Sciences, National Natural Science Foundation of China, Beijing 100085, China

Abstract

Diabetes is a major metabolic disease and health issue worldwide that imposes a heavy burden. Research on its pathogenesis and development of effective treatments are currently our major national demands. With the advent of organoid technology, islet organoids have emerged and are attracting increasing attention as a promising model for diabetes research. The establishment of islet organoids is based on the current understanding of islet development. With addition of extra induction factors in vitro to programmatically activate or inhibit specific signaling pathways during islet development, stem cells can be induced to differentiate into three-dimensional cell cultures that possess structures and functions similar to those of natural islets. Because of their capability to mimic the development of islets in vitro, faithfully replicate islet structure, and perform islet physiological functions, islet organoids have been widely used as a valuable tool for the investigation of diabetes pathogenesis, drug screening and evaluation, and clinical transplantation, showing a great potential application. This paper reviews the current research progress, application, and challenges of islet organoids, and discusses the future directions for research on islet organoids.

Key words: organoid; islet organoid; diabetes; research model; research progress

收稿日期：　　录用日期：

通讯作者：宋婀莉　　E-mail: songeli@nsfc.gov.cn

DOI: 10.13294/j.aps.2023.0071

引用本文：

宋婀莉, 王璞玥. 面向国家重大需求　开发建立新研究模型——胰岛类器官模型的研究进展与展望[J]. 生理学报 2024; 76 (1): 137-147.

SONG E-Li, WANG Pu-Yue. Focusing on the major national demands and developing novel research models——the research progress and prospective of islet organoid. Acta Physiol Sin 2024; 76 (1): 137-147 (in Chinese with English abstract).