National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Protein Cell. 2022 Apr;13(4):239-257. doi: 10.1007/s13238-021-00831-0. Epub 2021 Mar 10.
Studies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.
对糖尿病的研究长期以来一直受到缺乏真实疾病模型的阻碍，理想的疾病模型应该是无限的，并且能够重现人类胰腺胰岛在病理条件下的发育、结构和功能异常。基于干细胞的胰岛类器官在体外忠实地再现了胰岛的发育，并提供了大量具有与天然胰岛相似的形态结构和细胞组成的三维功能性胰岛仿生材料。因此，胰岛类器官在胰岛发育和功能建模、揭示糖尿病发病机制、为 SARS-CoV-2 等病毒的感染提供体外人类器官模型以及有助于药物筛选和自体胰岛移植方面具有巨大的应用前景。然而，与天然胰岛相比，目前建立的胰岛类器官通常还不够成熟，应该进一步努力提高胰岛类器官的异质性和功能性，使其成为一种真实的、具有信息性的糖尿病疾病模型。在这里，我们综述了胰岛类器官生成方面的进展和挑战，重点介绍了人多能干细胞衍生的胰岛类器官，以及胰岛类器官作为糖尿病疾病模型和再生治疗的潜在应用。
