Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation

Human liver stem cells (HLSCs) are a mesenchymal stromal cell-like population resident in the adult liver. Preclinical studies indicate that HLSCs could be a good candidate for cell therapy. The aim of the present study was to evaluate the immunogenicity and the immunomodulatory properties of HLSCs...

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Main Authors: Stefania Bruno, Cristina Grange, Marta Tapparo, Chiara Pasquino, Renato Romagnoli, Ennia Dametto, Antonio Amoroso, Ciro Tetta, Giovanni Camussi
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8468549
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author Stefania Bruno
Cristina Grange
Marta Tapparo
Chiara Pasquino
Renato Romagnoli
Ennia Dametto
Antonio Amoroso
Ciro Tetta
Giovanni Camussi
author_facet Stefania Bruno
Cristina Grange
Marta Tapparo
Chiara Pasquino
Renato Romagnoli
Ennia Dametto
Antonio Amoroso
Ciro Tetta
Giovanni Camussi
author_sort Stefania Bruno
collection DOAJ
description Human liver stem cells (HLSCs) are a mesenchymal stromal cell-like population resident in the adult liver. Preclinical studies indicate that HLSCs could be a good candidate for cell therapy. The aim of the present study was to evaluate the immunogenicity and the immunomodulatory properties of HLSCs on T-lymphocytes, natural killer cells (NKs), and dendritic cells (DCs) in allogeneic experimental settings. We found that HLSCs inhibited T-cell proliferation by a mechanism independent of cell contact and dependent on the release of prostaglandin E2 (PGE2) and on indoleamine 2,3-dioxygenase activity. When compared with mesenchymal stromal cells (MSCs), HLSCs were more efficient in inhibiting T-cell proliferation. At variance with MSCs, HLSCs did not elicit NK degranulation. Moreover, HLSCs inhibited NK degranulation against K562, a NK-sensitive target, by a mechanism dependent on HLA-G release. When tested on DC generation from monocytes, HLSCs were found to impair DC differentiation and DCs ability to induce T-cell proliferation through PGE2. This study shows that HLSCs have immunomodulatory properties similar to MSCs, but, at variance with MSCs, they do not elicit a NK response.
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issn 1687-966X
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publishDate 2016-01-01
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series Stem Cells International
spelling doaj-art-219adffd3c274f5baaa38e4085876a592025-02-03T05:44:51ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/84685498468549Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell DifferentiationStefania Bruno0Cristina Grange1Marta Tapparo2Chiara Pasquino3Renato Romagnoli4Ennia Dametto5Antonio Amoroso6Ciro Tetta7Giovanni Camussi8Department of Molecular Biotechnology and Health Science, University of Torino, 10126 Torino, ItalyDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyLiver Transplantation Center, University of Torino, Torino, ItalyRegional Transplantation Center, Piedmont, Molinette Hospital, Torino, ItalyDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyUnicyte AG, Oberdorf, SwitzerlandDepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyHuman liver stem cells (HLSCs) are a mesenchymal stromal cell-like population resident in the adult liver. Preclinical studies indicate that HLSCs could be a good candidate for cell therapy. The aim of the present study was to evaluate the immunogenicity and the immunomodulatory properties of HLSCs on T-lymphocytes, natural killer cells (NKs), and dendritic cells (DCs) in allogeneic experimental settings. We found that HLSCs inhibited T-cell proliferation by a mechanism independent of cell contact and dependent on the release of prostaglandin E2 (PGE2) and on indoleamine 2,3-dioxygenase activity. When compared with mesenchymal stromal cells (MSCs), HLSCs were more efficient in inhibiting T-cell proliferation. At variance with MSCs, HLSCs did not elicit NK degranulation. Moreover, HLSCs inhibited NK degranulation against K562, a NK-sensitive target, by a mechanism dependent on HLA-G release. When tested on DC generation from monocytes, HLSCs were found to impair DC differentiation and DCs ability to induce T-cell proliferation through PGE2. This study shows that HLSCs have immunomodulatory properties similar to MSCs, but, at variance with MSCs, they do not elicit a NK response.http://dx.doi.org/10.1155/2016/8468549
spellingShingle Stefania Bruno
Cristina Grange
Marta Tapparo
Chiara Pasquino
Renato Romagnoli
Ennia Dametto
Antonio Amoroso
Ciro Tetta
Giovanni Camussi
Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
Stem Cells International
title Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
title_full Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
title_fullStr Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
title_full_unstemmed Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
title_short Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation
title_sort human liver stem cells suppress t cell proliferation nk activity and dendritic cell differentiation
url http://dx.doi.org/10.1155/2016/8468549
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