Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells
Leite, Nayara C. ; Sintov, Elad ; Meissner, Torsten B. ; Brehm, Michael A. ; Greiner, Dale L. ; Harlan, David M. ; Melton, Douglas A.
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UMass Chan Affiliations
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Keywords
endoplasmic reticulum stress
induced pluripotent stem cell-derived β cells
type 1 diabetes
Cellular and Molecular Physiology
Disease Modeling
Endocrine System Diseases
Endocrinology
Endocrinology, Diabetes, and Metabolism
Immune System Diseases
Immunology and Infectious Disease
Nutritional and Metabolic Diseases
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Abstract
Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including beta cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells. We demonstrate a cell-type-specific response by autologous immune cells against induced pluripotent stem cell-derived beta cells, along with a reduced effect on alpha cells. This approach represents a path to developing disease models that use patient-derived cells to predict the outcome of an autoimmune response.
Source
Leite NC, Sintov E, Meissner TB, Brehm MA, Greiner DL, Harlan DM, Melton DA. Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells. Cell Rep. 2020 Jul 14;32(2):107894. doi: 10.1016/j.celrep.2020.107894. PMID: 32668238; PMCID: PMC7359783. Link to article on publisher's site