title: Enhanced expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocyte lineage.
abstract: The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for both albumin and tryptophan-2,3-dioxygenase was detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression of fibroblast growth factor 2 (FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for both albumin and tyrosine aminotransferase became detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.
authors.affiliation: Department of Gastroenterology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Haga
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugajin
authors.forename: Chikako
authors.initials: C
authors.lastname: Sato
authors.forename: Rika
authors.initials: R
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishise
authors.forename: Junitsu
authors.initials: J
authors.lastname: Ito
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Togashi
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2