title: Human liver cells expressing albumin and mesenchymal characteristics give rise to insulin-producing cells.
abstract: Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.
authors.affiliation: Sheba Regenerative Medicine, Stem cells and Tissue engineering Center, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Meivar-Levy
authors.forename: Tamar
authors.initials: T
authors.lastname: Sapir
authors.forename: Dana
authors.initials: D
authors.lastname: Berneman
authors.forename: Tal
authors.initials: T
authors.lastname: Weissbach
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakis
authors.forename: Eytan
authors.initials: E
authors.lastname: Mor
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Sarah
authors.initials: S
authors.lastname: Ferber