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Upregulation of sodium taurocholate cotransporter polypeptide during hepatogenic differentiation of umbilical cord matrix mesenchymal stem cells facilitates hepatitis B entry

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Sargiacomo, Camillo [UCL] El Kehdy, Hoda [UCL] Dallmeier, Kai de Kock, Joery Hernandez-Kelly, Clara Sokal, Etienne [UCL] Najimi, Mustapha [UCL]

BACKGROUND: Hepatitis B virus (HBV) carriers worldwide number approximately 240 million people and around 780,000 people die every year from HBV infection. HBV entry and uptake are functionally linked to the presence of the human sodium-taurocholate cotransporting peptide (hNTCP) receptor. Recently, our group demonstrated that human umbilical cord matrix stem cells (UCMSCs) become susceptible to HBV after in-vitro hepatogenic differentiation (D-UCMSCs). METHODS: In the present study, we examined the involvement of hNTCP in governing D-UCMSC susceptibility to HBV infection by characterizing the modulation of this transporter expression during hepatogenic differentiation and by appreciating the inhibition of its activity on infection efficacy. RESULTS: We show here that in-vitro hepatogenic differentiation upregulated hNTCP mRNA and protein expression as well as its activity in D-UCMSCs. Pre-treatment of D-UCMSCs with taurocholate, a specific NTCP substrate, blocked their infection by HBV which supports the crucial involvement of this transporter in the early steps of the virus entry. CONCLUSION: Altogether, our data support the usefulness of D-UCMSCs as a unique human and non-transformed in-vitro model to study the early stages of HBV infection thanks to its ability to endogenously regulate the expression of hNTCP.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Stem Cell Research & Therapy" - Vol. 8, no. 1, p. 204 [1-11] (2017)
Peer reviewed yes
Publisher BioMed Central ((United Kingdom) London)
e-issn 1757-6512
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
Links
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Bibliographic reference Sargiacomo, Camillo ; El Kehdy, Hoda ; Dallmeier, Kai ; de Kock, Joery ; Hernandez-Kelly, Clara ; et. al. Upregulation of sodium taurocholate cotransporter polypeptide during hepatogenic differentiation of umbilical cord matrix mesenchymal stem cells facilitates hepatitis B entry. In: Stem Cell Research & Therapy, Vol. 8, no. 1, p. 204 [1-11] (2017)
Permanent URL http://hdl.handle.net/2078.1/188849