title: Insulin-like growth factor 1 (IGF-I) improves hepatic differentiation of human bone marrow-derived mesenchymal stem cells.
abstract: The ability of MSCs (mesenchymal stem cells) to differentiate between other cell types makes these cells an attractive therapeutic tool for cell transplantation. This project was designed to improve transdifferentiation of human MSCs into liver cells using IGF-I (insulin-like growth factor 1) which, despite its important role in liver development, has not been used for in vitro hepatic differentiation. In the present study, the MSCs derived from healthy human bone marrow samples were cultured and characterized by immunophenotyping and differentiation potential into osteoblast and adipocytes. Transdifferentiation into hepatocyte-like cells was performed in the presence/absence of IGF-I in combination with predefined hepatic differentiation cocktail. To evaluate transdifferentiation, morphological features, immuno-cytochemical staining of specific biological markers and hepatic functions were assessed. Morphological assessment and evaluation of glycogen content, albumin and AFP (α-feto protein) expression as well as albumin and urea secretion revealed statistically significant difference between experimental groups compared with the control. Morphology and function (albumin secretion) of IGF-I-treated cells were significantly better than IGF-I-free experimental group. To the best of our knowledge, our study is the first to demonstrate that the combination of IGF-I with the predefined hepatic differentiation cocktail will significantly improve the morphological features of the differentiated cells and albumin secretion.
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. ayatollmb@yahoo.com
authors.forename: Maryam
authors.initials: M
authors.lastname: Ayatollahi
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.forename: Mohammad Hadi
authors.initials: MH
authors.lastname: Imanieh
mesh_terms: D000328:Adult; D000418:Albumins / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D005434:Flow Cytometry; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008875:Middle Aged; D010012:Osteogenesis; D013997:Time Factors; D014508:Urea / Q000378:metabolism; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D000418:Albumins; D015415:Biomarkers; D003470:Culture Media; D000509:alpha-Fetoproteins; D007334:Insulin-Like Growth Factor I; D014508:Urea; D006003:Glycogen