Pancreatic Pseudoislets: An Organoid Archetype for Metabolism Research
Pancreatic Pseudoislets: An Organoid Archetype for Metabolism Research
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DOI：
10.2337/db20-1115
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发表时间：
2021-05-01
期刊：
影响因子：
7.7
通讯作者：
Bevacqua, Romina J.
中科院分区：
文献类型：
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作者：
Friedlander, Mollie S. H.;Nguyen, Vy M.;Bevacqua, Romina J.
胰岛是全身代谢的重要内分泌调节因子，最近的研究越来越集中于了解人类胰岛生物学。对分离的人类胰岛的研究加深了对胰岛细胞（尤其是胰腺α细胞和β细胞）的发育、功能和调节的了解。然而，完整胰岛的多细胞性阻碍了特定的实验方法，特别是在遗传学和细胞信号传导研究方面。通过观察胰岛细胞可以在分散中存活并重新聚集形成“伪胰岛”，这一障碍已经被绕过，“伪胰岛”是保留重要生理功能（包括调节胰岛素和胰高血糖素分泌）的类器官。最近，世界各地的研究人员报道了使用伪胰岛进行遗传学、基因组学、胰岛细胞移植以及胰岛内信号传导和胰岛细胞相互作用的研究方面取得的令人兴奋的进展。在这里，我们回顾了促进胰岛细胞重新聚集的分子和细胞机制，总结了优化伪胰岛发育的方法，并详细介绍了基于遗传和移植的伪胰岛实验对人类胰岛生物学的最新见解。由于采购原代人类胰腺的强有力的国际计划，伪胰岛应成为原代类器官研究的持久范例，并作为胰岛生物学、糖尿病和代谢研究的发现引擎。
Pancreatic islets are vital endocrine regulators of systemic metabolism, and recent investigations have increasingly focused on understanding human islet biology. Studies of isolated human islets have advanced understanding of the development, function, and regulation of cells comprising islets, especially pancreatic alpha- and beta-cells. However, the multicellularity of the intact islet has stymied specific experimental approaches-particularly in genetics and cell signaling interrogation. This barrier has been circumvented by the observation that islet cells can survive dispersion and reaggregate to form "pseudoislets," organoids that retain crucial physiological functions, including regulated insulin and glucagon secretion. Recently, exciting advances in the use of pseudoislets for genetics, genomics, islet cell transplantation, and studies of intraislet signaling and islet cell interactions have been reported by investigators worldwide. Here we review molecular and cellular mechanisms thought to promote islet cell reaggregation, summarize methods that optimize pseudoislet development, and detail recent insights about human islet biology from genetic and transplantation-based pseudoislet experiments. Owing to robust, international programs for procuring primary human pancreata, pseudoislets should serve as both a durable paradigm for primary organoid studies and as an engine of discovery for islet biology, diabetes, and metabolism research.