Article (Scientific journals)
Human liver stem cells improve liver injury in a model of fulminant liver failure
Herrera, Maria Beatriz; Fonsato, Valentina; Bruno, Stefania et al.
2013In Hepatology, 57 (1), p. 311 - 319
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Abstract :
[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 :
Surgery
Author, co-author :
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
Language :
English
Title :
Human liver stem cells improve liver injury in a model of fulminant liver failure
Publication date :
2013
Journal title :
Hepatology
ISSN :
0270-9139
eISSN :
1527-3350
Publisher :
John Wiley & Sons, Hoboken, Us nj
Volume :
57
Issue :
1
Pages :
311 - 319
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 January 2024

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