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Differentiated umbilical cord matrix stem cells as a new in vitro model to study early events during HBV infection

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Paganelli, Massimiliano [UCL] Dallmeier, K. [Katholieke Universiteit Leuven] Nyabi, Omar [UCL] scheers, Isabelle [UCL] Kabamba, B. [UCL] Goubau, Patrick [UCL] Najimi, Mustapha [UCL] Sokal, Etienne [UCL]

The role of cell differentiation state on HBV replication has been well demonstrated, whereas how it determines cell susceptibility to HBV entry is far less understood. We previously showed that umbilical cord matrix stem cells (UCMSC) can be differentiated towards hepatocyte-like cells in vitro. In this study, we infected undifferentiated (UD-) and differentiated (D-) UCMSCs with HBV and studied infection kinetics comparing them to primary human hepatocytes (PHHs). UD-UCMSCs, although being permissive to viral binding, had a very limited uptake capacity, whereas D-UCMSCs showed binding and uptake capabilities similar to PHHs. Likewise, asialoglycoprotein receptor (ASGPR) was upregulated in UCMSCs upon differentiation. In D-UCMSCs, a dose-dependent inhibition of HBV binding and uptake was observed when ASGPR was saturated with known specific ligands. Subsequent viral replication was shown in D-UCMSCs but not in UD-UCMSCs. Susceptibility of UCMSCs to viral replication correlated with the degree of differentiation. Replication efficiency was low compared to PHHs, but was confirmed by (i) a dose-dependent inhibition by specific antiviral treatment using tenofovir, (ii) the increase of viral RNAs along time, (iii) de novo synthesis of viral proteins and (iv) secretion of infectious viral progeny. CONCLUSIONS: UCMSCs are turned permissive to support the entire HBV life cycle upon in vitro hepatic differentiation. Despite low replication efficiency, D-UCMSCs proved to be fully capable of HBV uptake. Overall, UCMSCs are a unique human, easily available, non-transformed, in vitro model of HBV infection that could prove useful to study early infection events and the role of cell differentiation state on such events. (HEPATOLOGY 2012.).

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2013
Language Anglais
Journal information "Hepatology" - Vol. 57, no. 1, p. 59-69 (2013)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken)
issn 0270-9139
e-issn 1527-3350
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale
UCL - (SLuc) Service de microbiologie
Links
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Bibliographic reference Paganelli, Massimiliano ; Dallmeier, K. ; Nyabi, Omar ; scheers, Isabelle ; Kabamba, B. ; et. al. Differentiated umbilical cord matrix stem cells as a new in vitro model to study early events during HBV infection. In: Hepatology, Vol. 57, no. 1, p. 59-69 (2013)
Permanent URL http://hdl.handle.net/2078.1/115538