Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells

The use of primary cells in human liver therapy is limited by a lack of cells. Induced pluripotent stem cells (iPSCs) represent an alternative to primary cells as they are infinitely expandable and can be differentiated into different liver cell types. The aim of our work was to demonstrate that sim...

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Main Authors: Eleanor Luce, Clara Steichen, Soumeya Abed, Anne Weber, Philippe Leboulch, Leila Maouche-Chrétien, Anne Dubart-Kupperschmitt
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/18/10861
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author Eleanor Luce
Clara Steichen
Soumeya Abed
Anne Weber
Philippe Leboulch
Leila Maouche-Chrétien
Anne Dubart-Kupperschmitt
author_facet Eleanor Luce
Clara Steichen
Soumeya Abed
Anne Weber
Philippe Leboulch
Leila Maouche-Chrétien
Anne Dubart-Kupperschmitt
author_sort Eleanor Luce
collection DOAJ
description The use of primary cells in human liver therapy is limited by a lack of cells. Induced pluripotent stem cells (iPSCs) represent an alternative to primary cells as they are infinitely expandable and can be differentiated into different liver cell types. The aim of our work was to demonstrate that simian iPSCs (siPSCs) could be used as a new source of liver cells to be used as a large animal model for preclinical studies. We first differentiated siPSCs into a homogenous population of hepatoblasts (siHBs). We then separately differentiated them into hepatocytes (siHeps) and cholangiocytes (siChols) expressing respective specific markers and displaying epithelial polarity. Moreover, we showed that polarized siChols can self-organize into 3D structures. These results should facilitate the deciphering of liver development and open the way to exploring co-culture systems that could be assessed during preclinical studies, including in autologous monkey donors, for regenerative medicine purposes.
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spelling doaj.art-0979766a90944985b5220e9f24868ba52023-11-23T16:49:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181086110.3390/ijms231810861Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem CellsEleanor Luce0Clara Steichen1Soumeya Abed2Anne Weber3Philippe Leboulch4Leila Maouche-Chrétien5Anne Dubart-Kupperschmitt6Unité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, FranceUnité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, FranceDivision of Innovative Therapies, Institute of Biology François Jacob, INSERM, Paris-Saclay University, CEA Fontenay aux Roses, F-92260 Fontenay-aux-Roses, FranceUnité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, FranceDivision of Innovative Therapies, Institute of Biology François Jacob, INSERM, Paris-Saclay University, CEA Fontenay aux Roses, F-92260 Fontenay-aux-Roses, FranceDivision of Innovative Therapies, Institute of Biology François Jacob, INSERM, Paris-Saclay University, CEA Fontenay aux Roses, F-92260 Fontenay-aux-Roses, FranceUnité Mixte de Recherche (UMR_S) 1193, INSERM/Université Paris-Saclay, F-94800 Villejuif, FranceThe use of primary cells in human liver therapy is limited by a lack of cells. Induced pluripotent stem cells (iPSCs) represent an alternative to primary cells as they are infinitely expandable and can be differentiated into different liver cell types. The aim of our work was to demonstrate that simian iPSCs (siPSCs) could be used as a new source of liver cells to be used as a large animal model for preclinical studies. We first differentiated siPSCs into a homogenous population of hepatoblasts (siHBs). We then separately differentiated them into hepatocytes (siHeps) and cholangiocytes (siChols) expressing respective specific markers and displaying epithelial polarity. Moreover, we showed that polarized siChols can self-organize into 3D structures. These results should facilitate the deciphering of liver development and open the way to exploring co-culture systems that could be assessed during preclinical studies, including in autologous monkey donors, for regenerative medicine purposes.https://www.mdpi.com/1422-0067/23/18/10861simian induced pluripotent stem cellshepatocyte differentiationcholangiocyte differentiation
spellingShingle Eleanor Luce
Clara Steichen
Soumeya Abed
Anne Weber
Philippe Leboulch
Leila Maouche-Chrétien
Anne Dubart-Kupperschmitt
Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
International Journal of Molecular Sciences
simian induced pluripotent stem cells
hepatocyte differentiation
cholangiocyte differentiation
title Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
title_full Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
title_fullStr Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
title_full_unstemmed Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
title_short Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
title_sort successful derivation of hepatoblasts cholangiocytes and hepatocytes from simian induced pluripotent stem cells
topic simian induced pluripotent stem cells
hepatocyte differentiation
cholangiocyte differentiation
url https://www.mdpi.com/1422-0067/23/18/10861
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