title: Hepatocytic Differentiation Potential of Human Fetal Liver Mesenchymal Stem Cells: In Vitro and In Vivo Evaluation.
abstract: In line with the search of effective stem cell population that would progress liver cell therapy and because the rate and differentiation potential of mesenchymal stem cells (MSC) decreases with age, the current study investigates the hepatogenic differentiation potential of human fetal liver MSCs (FL-MSCs). After isolation from 11-12 gestational weeks' human fetal livers, FL-MSCs were shown to express characteristic markers such as CD73, CD90, and CD146 and to display adipocytic and osteoblastic differentiation potential. Thereafter, we explored their hepatocytic differentiation potential using the hepatogenic protocol applied for adult human liver mesenchymal cells. FL-MSCs differentiated in this way displayed significant features of hepatocyte-like cells as demonstrated in vitro by the upregulated expression of specific hepatocytic markers and the induction of metabolic functions including CYP3A4 activity, indocyanine green uptake/release, and glucose 6-phosphatase activity. Following transplantation, naive and differentiated FL-MSC were engrafted into the hepatic parenchyma of newborn immunodeficient mice and differentiated in situ. Hence, FL-MSCs appeared to be interesting candidates to investigate the liver development at the mesenchymal compartment level. Standardization of their isolation, expansion, and differentiation may also support their use for liver cell-based therapy development.
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France.
authors.forename: Hoda
authors.identifier: 0000-0003-1731-0905
authors.initials: H
authors.lastname: El-Kehdy
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France; Département de Chirurgie Digestive Minimale-Invasive, Hôpital Antoine Béclère, APHP, 92141 Clamart, France.
authors.forename: Guillaume
authors.identifier: 0000-0001-9788-628X
authors.initials: G
authors.lastname: Pourcher
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France.
authors.forename: Wenwei
authors.identifier: 0000-0003-2719-6579
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France.
authors.forename: Zahia
authors.initials: Z
authors.lastname: Hamidouche
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France.
authors.forename: Sylvie
authors.identifier: 0000-0001-7919-3498
authors.initials: S
authors.lastname: Goulinet-Mainot
authors.affiliation: Université Catholique de Louvain, Institut de Recherche Expérimentale and Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, 1200 Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France; Pierre and Marie Curie University, IBPS Laboratory of Developmental Biology, UMR CNRS 7622, INSERM U1156, 75005 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charbord
authors.affiliation: Université Catholique de Louvain, Institut de Recherche Expérimentale and Clinique (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, 1200 Brussels, Belgium.
authors.forename: Mustapha
authors.identifier: 0000-0002-7329-9635
authors.initials: M
authors.lastname: Najimi
authors.affiliation: Inserm U972, Paul Brousse Hospital, 94807 Villejuif, France; UMR_S972, Université Paris-Sud, 94807 Villejuif, France; Département Hospitalo-Universitaire Hepatinov, Hôpital Paul Brousse, 94807 Villejuif, France.
authors.forename: Anne
authors.identifier: 0000-0002-9326-4413
authors.initials: A
authors.lastname: Dubart-Kupperschmitt