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Hepatocyte Growth Factor is the Key Cytokine in Stimulating Potential Stem Cells in the Cord Blood into Hepatic Lineage Cells

  • Ryu, Kyung-Ha (Department of Pediatrics Ewha Medical Research Institute, Ewha Womans University School of Medicine) ;
  • Cho, Su-Jin (Department of Pediatrics Ewha Medical Research Institute, Ewha Womans University School of Medicine) ;
  • Woo, So-Youn (Department of Microbiology, Ewha Medicial Research Institute, Ewha Womans University School of Medicine) ;
  • Seoh, Ju-Young (Department of Microbiology, Ewha Medicial Research Institute, Ewha Womans University School of Medicine) ;
  • Jung, Yun-Jae (Department of Microbiology, Gachon Medical School) ;
  • Han, Ho-Seong (Department of Surgery, Seoul National University College of Medicine)
  • Published : 2007.09.30
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Abstract

Background: This study was designed to investigate the role of the hepatocyte growth factor (HGF) with regards to differentiation of somatic stem cells originating from the human umbilical cord blood (UCB) into hepatic lineage cells in vitro culture system. Methods: Mononuclear cells from UCB were cultured with and without HGF based on the fibroblast growth factor (FGF)-1, FGF-2, and stem cell factor. The cultured cells were confirmed by immunofluorescent staining analysis with albumin (ALB), cytokeratin-19 (CK-19), and proliferating cell nuclear antigen (PCNA) MoAb. ALB and CK-18 mRNA were also evaluated by reverse transcription-polymerase chain reaction. In order to observe changes in proliferating capacity with respect to the cultured period, CFSE with affinity to proliferating cells were tagged and later underwent flow cytometry. Results: In the HGF-treated group, cultured cells had a large oval shaped appearance with adherent, but easily detachable characteristics. In the HGF-non treated group, these cells were spindle-shaped with strong adherent characteristics. Expressions of ALB and CK-19 were evident in HGF-treated group compared to non-expression of those in to HGF-non treated group. Dual immunostaining analysis of the ALB producing cells showed presence of PCNA in their nuclei, and ALB and CK-18 mRNA were detected on the 21st day of cultured cells in the HGF-treated group. Conclusion: Our findings suggest that HGF has a pivotal role in differentiating somatic stem cells of human UCB into hepatic lineage cells in vitro.

Keywords

References

  1. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP: Bone marrow as a potential source of hepatic oval cells. Science 284;1168-1170, 1999 https://doi.org/10.1126/science.284.5417.1168
  2. Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM: Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109;1291-1302, 2002 https://doi.org/10.1172/JCI0215182
  3. Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H: Human umbilical cord blood as a source of transplantable hepatic progenitor cell. Stem Cells 21;217-227, 2003 https://doi.org/10.1634/stemcells.21-2-217
  4. Ahdjoudj S, Lasmoles F, Oyajobi BO, Lomri A, Delannoy P, Marie PJ: Reciprocal control of osteoblast/chondroblast and osteoblast/adipocyte differentiation of rnultipotential clonal human marrow stromal F/STRO-l(+) cells. J Cell Biochem 1;23-38, 2001
  5. Atmani H, Chappard D, Basle MF: Proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures: effects of dexamethasone and calcitriol. J Cell Biochem 2;364-372, 2003
  6. Ryu KH, Yoo ES, Jung YJ, Woo SY, Lee MY, Seoh JY, Ahn HS, Yoo K, Han HS: Ex vivo expansion and differentiation of hepatocytes from human umbilical cord blood. Exp Hematol 32(S);265a, 2004
  7. Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M: Kinetics of liver repopulation after bone marrow transplantation. Am J Pathol 161;565-574, 2002 https://doi.org/10.1016/S0002-9440(10)64212-5
  8. Watt FM, Hogan B: Out of eden: srem cells and their niches. Science 287;1427-1430, 2000 https://doi.org/10.1126/science.287.5457.1427
  9. Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR, Fiegel HC: Liver-specific gene expression in mesenchymal stem cells is induced by liver cells. World J Gastroenterol 11;4497-4504, 2005 https://doi.org/10.3748/wjg.v11.i29.4497
  10. Akino K, Mineda T, Akita S: Early cellular changes of human mesenchymal stem cells and their interaction with other cells. Wound Repair Regen 13;434-440, 2005 https://doi.org/10.1111/j.1067-1927.2005.130411.x
  11. Tang LJ, Gao Y, Zhang Z, Li H, Shan YQ: Human bone marrow multipotent adult progenitor cells differentiate into hepatocyte-like cells with hepatocyte growth factor plus fibroblast growth factor-4 in vitro. Zhonghua Gan Zang Bing Za Zhi 13;652-655, 2005
  12. Hodgson H: C-met-there when it's needed? J Hepatol 43; 544-546, 2005 https://doi.org/10.1016/j.jhep.2005.06.004
  13. Xu C, Rosler E, Jiang J, Lebkowski JS, Gold JD, O'Sullivan C, Delavan-Boorsma K, Mok M, Bronstein A, Carpenter MK: Basic fibroblast growth factor supports undifferentiated human embryonic stem cell growth without conditioned medium. Stem Cells 23;315-323, 2005 https://doi.org/10.1634/stemcells.2004-0211
  14. Ishikawa T, Terai S, Urata Y, Marumoto Y, Aoyama K, Sakaida I, Murata T, Nishina H, Shinoda K, Uchimura S, Hamamoto Y, Okita K: Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes, Cell Tissue Res 14;1-11, 2005
  15. Nava S, Westgren M, Jaksch M, Tibell A, Broome U, Ericzon BG, Sumittan-Holgersson S: Characterization of cells in the developing human liver. Differentiation 73;249-260, 2005 https://doi.org/10.1111/j.1432-0436.2005.00019.x
  16. Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK: In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40;1275-1284, 2004 https://doi.org/10.1002/hep.20469
  17. Kang XQ, Zang WJ, Song TS, Xu XL, Yu XJ, Li DL, Meng KW, Wu SL, Zhao ZY: Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro. World J Gastroenterol 11;3479-3484, 2005 https://doi.org/10.3748/wjg.v11.i22.3479
  18. Knight B, Matthews VB, Olynyk JK, Yeoh GC: Jekyll and Hyde: Evolving perspectives on the function and potential of the adult liver progenitor (oval) cell. Bioessays 27;1192-1202, 2005 https://doi.org/10.1002/bies.20311
  19. Higuchi A, Kurihara M, Kobayashi K, Cho CS, Akaike T, Hara M: Albumin and urea production by hepatocytes cultured on extracellular matrix proteins-conjugated poly (vinyl alcohol) membranes. J Biomater Sci Polym Ed 16;847-860, 2005 https://doi.org/10.1163/1568562054255727
  20. Dvorak P, Dvorakova D, Koskova S, Vodinska M, Najvirtova M, Krekac D, Hampl A: Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells 23;1200-1211, 2005 https://doi.org/10.1634/stemcells.2004-0303
  21. Wang XQ, Duan XM, Liu LH, Fang YQ, Tan Y: Carboxyfluorescein diacetate succinimidyl ester fluorescent dye for cell labeling. Acta Biochim Biophys Sin 37;379-385, 2005 https://doi.org/10.1111/j.1745-7270.2005.00051.x