Human liver stem cells improve liver injury in a model of fulminant liver failure

[en] Liver transplantation is currently the only effective therapy for fulminant liver failure, but its use is limited by the scarcity of organs for transplantation, high costs, and lifelong immunosuppression. Here we investigated whether human liver stem cells (HLSCs) protect from death in a lethal model of fulminant liver failure induced by intraperitoneal injection of D-galactosamine and lipopolysaccharide in SCID mice. We show that injection of HLSCs and of HLSC-conditioned medium (CM) significantly attenuates mouse mortality in this model. Histopathological analysis of liver tissue showed reduction of liver apoptosis and enhancement of liver regeneration. By optical imaging we observed a preferential localization of labeled HLSCs within the liver. HLSCs were detected by immunohistochemistry in large liver vessels (at 24 hours) and in the liver parenchyma (after day 3). Fluorescence in situ hybridization analysis with the human pan-centromeric probe showed that positive cells were cytokeratin-negative at 24 hours. Coexpression of cytokeratin and human chromosome was observed at 7 and, to a lesser extent, at 21 days. HLSC-derived CM mimicked the effect of HLSCs in vivo. Composition analysis of the HLSC-CM revealed the presence of growth factors and cytokines with liver regenerative properties. In vitro experiments showed that HLSC-CM protected human hepatocytes from apoptosis and enhanced their proliferation. Conclusion: These data suggest that fulminant liver failure may potentially benefit from treatment with HLSCs or HLSC-CM. (HEPATOLOGY 2013) © 2012 American Association for the Study of Liver Diseases.

Disciplines :

Chirurgie

Auteur, co-auteur :

Herrera, Maria Beatriz; Department of Internal Medicine, Molecular Biotechnology Center, University of Turin, Italy ; Sis-Ter S.p.A., Palazzo Pignano (CR), Italy

Fonsato, Valentina; Department of Internal Medicine, Molecular Biotechnology Center, University of Turin, Italy

Bruno, Stefania; Department of Internal Medicine, Molecular Biotechnology Center, University of Turin, Italy

Grange, Cristina; Department of Internal Medicine, Molecular Biotechnology Center, University of Turin, Italy

Gilbo, NICHOLAS ; Université de Liège - ULiège > Département des sciences cliniques > Pathologie chirurgicale abdominale et endocrinienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation

Romagnoli, Renato; Liver Transplantation Center, University of Torino, Torino, Italy

Tetta, Ciro; Fresenius Medical Care, Bad Homburg, Germany

Camussi, Giovanni; Department of Internal Medicine, Molecular Biotechnology Center, University of Turin, Italy

Langue du document :

Anglais

Titre :

Human liver stem cells improve liver injury in a model of fulminant liver failure

Date de publication/diffusion :

2013

Titre du périodique :

Hepatology

ISSN :

0270-9139

eISSN :

1527-3350

Maison d'édition :

John Wiley & Sons, Hoboken, Us nj

Volume/Tome :

Fascicule/Saison :

Pagination :

311 - 319

Peer reviewed :

Peer reviewed vérifié par ORBi

Disponible sur ORBi :

depuis le 25 janvier 2024

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46 (dont 0 ULiège)

Nombre de téléchargements

1 (dont 0 ULiège)

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Bibliographie

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