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

Autor: Haq N; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Toczyska KW; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Wilson ME; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Jacobs M; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Zhao M; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Lei Y; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Shen Z; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Pearson JA; Diabetes Research Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK., Persaud SJ; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Pullen TJ; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK., Bewick GA; Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Diabetes Endocrinology and Obesity Clinical Academic Partnership, King's College London and King's Health Partners, Guy's Campus, London, UK. gavin.bewick@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Cell death discovery [Cell Death Discov] 2024 Nov 23; Vol. 10 (1), pp. 480. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1038/s41420-024-02234-6
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All animal experiments were approved by the King’s College London Animal Welfare and Ethical Review Board and were performed in accordance with the British Home Office Animal Scientific Procedures Act (1986). All human islets were retrieved from non-diabetic, heart-beating, and brain-dead donors and isolated by cold collagenase digestion [23, 61] in accordance with relevant guidelines and regulations with appropriate ethical approval from the King’s College London Human Islet Research Tissue Bank (KCL HI-RTB; 20/SW/0074). An assent form was completed by a relative of the pancreas donor for all the islets used in the study.
(© 2024. The Author(s).)
Databáze: MEDLINE
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