title: Mobilization of hepatic mesenchymal stem cells from human liver grafts.
abstract: Extensive studies have demonstrated the potential applications of bone marrow-derived mesenchymal stem cells (BM-MSCs) as regenerative or immunosuppressive treatments in the setting of organ transplantation. The aims of the present study were to explore the presence and mobilization of mesenchymal stem cells (MSCs) in adult human liver grafts and to compare their functional capacities to those of BM-MSCs. The culturing of liver graft preservation fluids (perfusates) or end-stage liver disease tissues resulted in the expansion of MSCs. Liver-derived mesenchymal stem cells (L-MSCs) were equivalent to BM-MSCs in adipogenic and osteogenic differentiation and in wingless-type-stimulated proliferative responses. Moreover, the genome-wide gene expression was very similar, with a 2-fold or greater difference found in only 82 of the 32,321 genes (0.25%). L-MSC differentiation into a hepatocyte lineage was demonstrated in immunodeficient mice and in vitro by the ability to support a hepatitis C virus infection. Furthermore, a subset of engrafted MSCs survived over the long term in vivo and maintained stem cell characteristics. Like BM-MSCs, L-MSCs were found to be immunosuppressive; this was shown by significant inhibition of T cell proliferation. In conclusion, the adult human liver contains an MSC population with a regenerative and immunoregulatory capacity that can potentially contribute to tissue repair and immunomodulation after liver transplantation.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Qiuwei
authors.initials: Q
authors.lastname: Pan
authors.forename: Suomi M G
authors.initials: SM
authors.lastname: Fouraschen
authors.forename: Fatima S F Aerts
authors.initials: FS
authors.lastname: Kaya
authors.forename: Monique M
authors.initials: MM
authors.lastname: Verstegen
authors.forename: Mario
authors.initials: M
authors.lastname: Pescatori
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Stubbs
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Antoine
authors.initials: A
authors.lastname: van der Sloot
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Geert
authors.initials: G
authors.lastname: Kazemier
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Jonge
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Gerard
authors.initials: G
authors.lastname: Wagemaker
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000166:cytology*; D016031:Liver Transplantation / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010012:Osteogenesis; D010477:Perfusion