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EndoC-βH5 cells are...
EndoC-βH5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion
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Blanchi, Bruno (author)
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Taurand, Marion (author)
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- Colace, Claire (author)
- Paris-Sorbonne University
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- Thomaidou, Sofia (author)
- Leiden University Medical Centre
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Audeoud, Charlotte (author)
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- Fantuzzi, Federica (author)
- University of Parma,Université Libre de Bruxelles (ULB)
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- Sawatani, Toshiaki (author)
- Université Libre de Bruxelles (ULB)
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- Gheibi, Sevda (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Sabadell-Basallote, Joan (author)
- Hospital Joan XXIII,Harvard Medical School
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- Boot, Fransje W.J. (author)
- Leiden University Medical Centre
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Chantier, Thibault (author)
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Piet, Aline (author)
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Cavanihac, Charlotte (author)
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Pilette, Marion (author)
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Balguerie, Adélie (author)
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Olleik, Hamza (author)
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- Carlotti, Françoise (author)
- Leiden University Medical Centre
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- Ejarque, Miriam (author)
- Hospital Joan XXIII
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- Fex, Malin (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Cnop, Miriam (author)
- Université Libre de Bruxelles (ULB)
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- Eizirik, Decio L. (author)
- Université Libre de Bruxelles (ULB)
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Jouannot, Ouardane (author)
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Gaffuri, Anne Lise (author)
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Czernichow, Paul (author)
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- Zaldumbide, Arnaud (author)
- Leiden University Medical Centre
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- Scharfmann, Raphaël (author)
- Institut Cochin
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- Ravassard, Philippe (author)
- Paris-Sorbonne University
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Molecular Metabolism. - 2212-8778. ; 76
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Glucose and incretin stimulated insulin secretion
- Human beta cell function
- Human pancreatic beta cell line
- Type-I diabetes disease model
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Blanchi, Bruno
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Taurand, Marion
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Colace, Claire
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Thomaidou, Sofia
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Audeoud, Charlot ...
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Fantuzzi, Federi ...
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show more...
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Sawatani, Toshia ...
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Gheibi, Sevda
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Sabadell-Basallo ...
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Boot, Fransje W. ...
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Chantier, Thibau ...
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Piet, Aline
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Cavanihac, Charl ...
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Pilette, Marion
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Balguerie, Adéli ...
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Olleik, Hamza
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Carlotti, Franço ...
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Ejarque, Miriam
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Fex, Malin
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Mulder, Hindrik
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Cnop, Miriam
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Eizirik, Decio L ...
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Jouannot, Ouarda ...
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Gaffuri, Anne Li ...
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Czernichow, Paul
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Zaldumbide, Arna ...
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Scharfmann, Raph ...
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Ravassard, Phili ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Molecular Metabo ...
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Lund University