PMID- 21152936 OWN - NLM STAT- MEDLINE DCOM- 20110624 LR - 20110202 IS - 1432-0878 (Electronic) IS - 0302-766X (Linking) VI - 343 IP - 2 DP - 2011 Feb TI - 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. PG - 371-8 LID - 10.1007/s00441-010-1093-2 [doi] AB - 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. FAU - Haga, Hiroaki AU - Haga H AD - Department of Gastroenterology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan. FAU - Saito, Takafumi AU - Saito T FAU - Okumoto, Kazuo AU - Okumoto K FAU - Ugajin, Satoshi AU - Ugajin S FAU - Sato, Chikako AU - Sato C FAU - Ishii, Rika AU - Ishii R FAU - Nishise, Yuko AU - Nishise Y FAU - Ito, Junitsu AU - Ito J FAU - Watanabe, Hisayoshi AU - Watanabe H FAU - Saito, Koji AU - Saito K FAU - Togashi, Hitoshi AU - Togashi H FAU - Kawata, Sumio AU - Kawata S LA - eng PT - Journal Article DEP - 20101209 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (RNA, Messenger) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology/metabolism MH - *Cell Differentiation MH - *Cell Lineage MH - Cell Proliferation MH - Epithelial Cells/cytology/*metabolism MH - Fibroblast Growth Factor 2/genetics/*metabolism MH - Hepatocytes/*cytology/metabolism MH - Male MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Stem Cells/*cytology/metabolism EDAT- 2010/12/15 06:00 MHDA- 2011/06/28 06:00 CRDT- 2010/12/15 06:00 PHST- 2010/08/04 00:00 [received] PHST- 2010/11/17 00:00 [accepted] PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2011/06/28 06:00 [medline] AID - 10.1007/s00441-010-1093-2 [doi] PST - ppublish SO - Cell Tissue Res. 2011 Feb;343(2):371-8. doi: 10.1007/s00441-010-1093-2. Epub 2010 Dec 9.