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Endocrine Abstracts (2015) 37 S22.3 | DOI: 10.1530/endoabs.37.S22.3

ECE2015 Symposia Beta cell biology (3 abstracts)

Novel models of human pancreatic beta cells

Philippe Ravassard


ICM, CNRS UMR 7225, Paris, France.


Despite intense efforts over the past decades, human pancreatic beta cell lines with physiological insulin secretion have not been available. We have developed a robust transplantation model of fetal human pancreases that recapitulates pancreas development and combined such model with integrative lentiviral-mediated gene transfer. This resulted in production of human transgenic pancreases in which dynamic aspects of development can be studied. We thus forced expression of immortalizing transgene in developing human beta cells and were able to produce the first and only functional human beta cell lines. Importantly, such lines secrete insulin in response to glucose and are able to revert chemically induced diabetes in mice upon transplantation. Furthermore, we derived a conditionally immortalized human pancreatic β cell line using Cre-dependent reversible immortalization. After massive amplification immortalizing transgenes are removed resulting in proliferation arrest and dramatic enhancement of beta cell function. Altogether, these cells lines represent unique tools to study beta cell biology studies, for drug discovery and as preclinical model for cell replacement therapy.

Disclosure: Research was supported by CNRS, INSERM and Endocells and by grants from the Seventh Framework Program of the European Union (no. 241883), from the Innovative Medicines Initiative Joint Undertaking under grant agreement (no. 155005; IMIDIA).

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