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Development of a conditionally immortalized human pancreatic β cell line

Abstract : Diabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little is known about the factors that regulate proliferation of these cells in human pancreas. Access to primary human β cells is limited and a challenge for both functional studies and drug discovery progress. We previously reported the generation of a human β cell line (EndoC-βH1) that was generated from human fetal pancreas by targeted oncogenesis followed by in vivo cell differentiation in mice. EndoC-βH1 cells display many functional properties of adult β cells, including expression of β cell markers and insulin secretion following glucose stimulation; however, unlike primary β cells, EndoC-βH1 cells continuously proliferate. Here, we devised a strategy to generate conditionally immortalized human β cell lines based on Cre-mediated excision of the immortalizing transgenes. The resulting cell line (EndoC-βH2) could be massively amplified in vitro. After expansion, transgenes were efficiently excised upon Cre expression, leading to an arrest of cell proliferation and pronounced enhancement of β cell–specific features such as insulin expression, content, and secretion. Our data indicate that excised EndoC-βH2 cells are highly representative of human β cells and should be a valuable tool for further analysis of human β cells.
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Raphaël Scharfmann, Severine Pechberty, Yasmine Hazhouz, Manon von Bülow, Emilie Bricout-Neveu, et al.. Development of a conditionally immortalized human pancreatic β cell line. Journal of Clinical Investigation, American Society for Clinical Investigation, 2014, 124 (5), pp.2087-2098. ⟨10.1172/JCI72674⟩. ⟨hal-01329344⟩

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