Reformed islets: a long-term primary cell platform for exploring mouse and human islet biology

TY - JOUR

T1 - Reformed islets

T2 - a long-term primary cell platform for exploring mouse and human islet biology

AU - Haq, N

AU - Toczyska, K W

AU - Wilson, M E

AU - Jacobs, M

AU - Zhao, Min

AU - Lei, Y

AU - Shen, Z

AU - Pearson, J A

AU - Persaud, S J

AU - Pullen, T J

AU - Bewick, G A

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/11/23

Y1 - 2024/11/23

N2 - Pancreatic islets are 3D micro-organs that maintain β-cell functionality through cell–cell and cell-matrix communication. While primary islets, the gold standard for in vitro models, have a short culture life of approximately 1–2 weeks, we developed a novel protocol that employs reformed islets following dispersion coupled with a fine-tuned culture environment. Reformed islets exhibit physiological characteristics similar to primary islets, enabling high-resolution imaging and repeated functional assessment. Unlike other in vitro platforms, reformed islets retain an immune population, allowing the study of interactions between β cells and resident and infiltrating immune cells. Analyses showed that reformed islets have a similar composition and cytoarchitecture to primary islets, including macrophages and T cells, and can secrete insulin in response to glucose. Reformed islets exhibited partial dedifferentiation compared to native islets but were otherwise transcriptionally similar. The reformed islets offer a useful platform for studying diabetes pathology and can recapitulate both T1DM and T2DM disease milieus, providing an advantage over other models, such as mouse and human β-cell lines, which lack the input of non-β-endocrine cells and immune cell crosstalk. (Figure presented.)

AB - Pancreatic islets are 3D micro-organs that maintain β-cell functionality through cell–cell and cell-matrix communication. While primary islets, the gold standard for in vitro models, have a short culture life of approximately 1–2 weeks, we developed a novel protocol that employs reformed islets following dispersion coupled with a fine-tuned culture environment. Reformed islets exhibit physiological characteristics similar to primary islets, enabling high-resolution imaging and repeated functional assessment. Unlike other in vitro platforms, reformed islets retain an immune population, allowing the study of interactions between β cells and resident and infiltrating immune cells. Analyses showed that reformed islets have a similar composition and cytoarchitecture to primary islets, including macrophages and T cells, and can secrete insulin in response to glucose. Reformed islets exhibited partial dedifferentiation compared to native islets but were otherwise transcriptionally similar. The reformed islets offer a useful platform for studying diabetes pathology and can recapitulate both T1DM and T2DM disease milieus, providing an advantage over other models, such as mouse and human β-cell lines, which lack the input of non-β-endocrine cells and immune cell crosstalk. (Figure presented.)

UR - http://www.scopus.com/inward/record.url?scp=85209916040&partnerID=8YFLogxK

U2 - 10.1038/s41420-024-02234-6

DO - 10.1038/s41420-024-02234-6

M3 - Article

C2 - 39580467

SN - 2058-7716

VL - 10

SP - 480

JO - Cell Death Discovery

JF - Cell Death Discovery

IS - 1

M1 - 480

ER -