Pancreatic Pseudoislets: An Organoid Archetype for Metabolism Research

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.

Automated summary

Recent studies have focused on understanding human islet biology, with advances in isolated human islet research providing insights into the development and function of islet cells. By dispersing and reaggregating islet cells to form pseudoislets, specific experimental approaches have been facilitated, leading to exciting new discoveries in genetics, genomics, and islet cell transplantation. The use of pseudoislets is contributing to significant progress in the study of islet biology, diabetes, and metabolism.