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

Autor: N. Haq, K. W. Toczyska, M. E. Wilson, M. Jacobs, Min Zhao, Y. Lei, Z. Shen, J. A. Pearson, S. J. Persaud, T. J. Pullen, G. A. Bewick
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Death Discovery, Vol 10, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-024-02234-6
Popis: 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.
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