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

Haq, N., Toczyska, K. W., Wilson, M. E., Jacobs, M., Zhao, Min, Lei, Y., Shen, Z., Pearson, J. A. ORCID: https://orcid.org/0000-0002-2867-2269, Persaud, S. J., Pullen, T. J. and Bewick, G. A. 2024. Reformed islets: a long-term primary cell platform for exploring mouse and human islet biology. Cell Death Discovery 10 , 480. 10.1038/s41420-024-02234-6

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	2058-7716
Date of First Compliant Deposit:	26 November 2024
Date of Acceptance:	30 October 2024
Last Modified:	26 Nov 2024 11:16
URI:	https://orca.cardiff.ac.uk/id/eprint/174303

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