EndoC-βH5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion.

Autor:	Blanchi B; Human Cell Design, Canceropole, Toulouse, France. Electronic address: b.blanchi@humancelldesign.com., Taurand M; Human Cell Design, Canceropole, Toulouse, France., Colace C; Paris Brain Institute, Sorbonne Université, Inserm U1127, CNRS UMR 7225, Paris, France., Thomaidou S; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., Audeoud C; Adocia, Lyon, France., Fantuzzi F; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium; Department of Medicine and Surgery, University of Parma, Parma, Italy., Sawatani T; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium., Gheibi S; Department of Clinical Sciences, Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö, Sweden., Sabadell-Basallote J; Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Tarragona, Spain; Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Boot FWJ; Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands., Chantier T; Adocia, Lyon, France., Piet A; Human Cell Design, Canceropole, Toulouse, France., Cavanihac C; Human Cell Design, Canceropole, Toulouse, France., Pilette M; Human Cell Design, Canceropole, Toulouse, France., Balguerie A; Human Cell Design, Canceropole, Toulouse, France., Olleik H; Human Cell Design, Canceropole, Toulouse, France., Carlotti F; Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands., Ejarque M; Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Tarragona, Spain., Fex M; Department of Clinical Sciences, Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö, Sweden., Mulder H; Department of Clinical Sciences, Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö, Sweden., Cnop M; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium., Eizirik DL; ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium., Jouannot O; Adocia, Lyon, France., Gaffuri AL; Adocia, Lyon, France., Czernichow P; Animal Cell Therapy, Paris, France., Zaldumbide A; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands., Scharfmann R; Université Paris Cité, Institut Cochin, CNRS, INSERM U1016, Paris, 75014, France., Ravassard P; Paris Brain Institute, Sorbonne Université, Inserm U1127, CNRS UMR 7225, Paris, France. Electronic address: philippe.ravassard@icm-institute.org.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2023 Oct; Vol. 76, pp. 101772. Date of Electronic Publication: 2023 Jul 11.
DOI:	10.1016/j.molmet.2023.101772
Abstrakt:	Objectives: Readily accessible human pancreatic beta cells that are functionally close to primary adult beta cells are a crucial model to better understand human beta cell physiology and develop new treatments for diabetes. We here report the characterization of EndoC-βH5 cells, the latest in the EndoC-βH cell family. Methods: EndoC-βH5 cells were generated by integrative gene transfer of immortalizing transgenes hTERT and SV40 large T along with Herpes Simplex Virus-1 thymidine kinase into human fetal pancreas. Immortalizing transgenes were removed after amplification using CRE activation and remaining non-excized cells eliminated using ganciclovir. Resulting cells were distributed as ready to use EndoC-βH5 cells. We performed transcriptome, immunological and extensive functional assays. Results: Ready to use EndoC-βH5 cells display highly efficient glucose dependent insulin secretion. A robust 10-fold insulin secretion index was observed and reproduced in four independent laboratories across Europe. EndoC-βH5 cells secrete insulin in a dynamic manner in response to glucose and secretion is further potentiated by GIP and GLP-1 analogs. RNA-seq confirmed abundant expression of beta cell transcription factors and functional markers, including incretin receptors. Cytokines induce a gene expression signature of inflammatory pathways and antigen processing and presentation. Finally, modified HLA-A2 expressing EndoC-βH5 cells elicit specific A2-alloreactive CD8 T cell activation. Conclusions: EndoC-βH5 cells represent a unique storable and ready to use human pancreatic beta cell model with highly robust and reproducible features. Such cells are thus relevant for the study of beta cell function, screening and validation of new drugs, and development of disease models. Competing Interests: Declaration of Competing Interest BB, MT, AP, CC, MP, AB and HO are or were employees at Human Cell Design SA, France, the company that commercializes EndoC-βH1 and EndoC-βh5 cells and associated media. RS, PC and PR are shareholders at HCD. (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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