Leukemia inhibitory factor contributes to hepatocyte-like differentiation of human bone marrow mesenchymal stem cells.
The current majority of protocols for hepatocyte differentiation of mesenchymal stem cells (MSCs) are conducted using oncostatin M (OSM) as an inducer of hepatocyte-like maturation. As leukemia inhibitory factor (LIF) and OSM share similar signaling pathways, we examined whether LIF could play a role in the hepatocyte differentiation process. A differentiation protocol was designed using LIF as a maturation cytokine and this was compared with standard and control protocols applied to human MSCs of bone marrow origin. We observed that mesenchymal-derived hepatocyte-like cells (MDHLCs) acquired similar morphological changes when exposed to LIF or to OSM. Using protein and gene expression assays, we noticed a comparable hepatic marker expression in both differentiation conditions. Furthermore, LIF and OSM allowed the acquisition of equivalent levels of hepatocyte-like functionality as attested by evaluation of urea secretion and glycogen deposition. However, no increase in the expression of hepatocyte-like features could be observed in MDHLCs after a combined exposition to LIF and OSM. In conclusion, we demonstrated that LIF can play a similar role as OSM in the hepatocyte differentiation process of human MSCs.
HPED Department, PEDI Unit, Université Catholique de Louvain, Cliniques Universitaires Saint Luc, Brussels, Belgium. philippe.lysy@pedi.ucl.ac.be
Philippe A
PA
Lysy
Françoise
F
Smets
Mustapha
M
Najimi
Etienne M
EM
Sokal
D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D053683:Oncostatin M / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
D006131:Growth Inhibitors; D053605:Leukemia Inhibitory Factor; D053683:Oncostatin M