한국간담췌외과학회지 (Annals of Hepato-Biliary-Pancreatic Surgery)

  • 제13권4호
  • /
  • Pages.205-214
  • /
  • 2009
  • /
  • 2508-5778(pISSN)
  • /
  • 2508-5859(eISSN)
한국간담췌외과학회 (The Korean Association of Hepato-Biliary-Pancreatic Surgery)
권호 표지

Activin A를 이용한 지방 유래 간엽줄기세포의 내배엽 분화 유도 증진

Mesenchymal Stem Cells: The Promotion of Endodermal-Induction Using Activin A

  • 이상우 (연세대학교 의과대학 외과학교실) ;
  • 민선옥 (연세대학교 의과대학 외과학교실) ;
  • 김신영 (연세대학교 의과대학 진단검사의학교실) ;
  • 최새별 (고려대학교 의과대학 외과학교실) ;
  • 김현옥 (연세대학교 의과대학 진단검사의학교실) ;
  • 김경식 (연세대학교 의과대학 외과학교실)
  • Lee, Sang-Woo (Department of Surgery, Yonsei University College of Medicine) ;
  • Min, Seon-Ok (Department of Surgery, Yonsei University College of Medicine) ;
  • Kim, Shin-Young (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Choi, Sae-Byeo (Department of surgery Korea University College of Medicine) ;
  • Kim, Hyun-Ok (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Kim, Kyung-Sik (Department of Surgery, Yonsei University College of Medicine)
  • 발행 : 2009.12.31

⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: The most important consideration for therapy using MSCs is the differentiation of the target organ's cell type. For in-vitro hepatogenic differentiation of MSCs, the main focus is efficient induction of the MSCs into the endoderm stage. Activin A, which is a signaling molecule that is similar to Nodal, promotes the induction of definitive endoderm from both ESs and MSCs. The protocols for induction into definitive endoderm have shown different efficiency and reproducibility depending on the researchers or the sources of the MSCs. Thus, a study on the various conditions of Activin A is needed to efficiently differentiate MSCs into the definitive endoderm lineage of MSCs. Methods: MSCs were isolated from human adipose tissues and these were cultured in MCM (MSCs Culture Medium) on a human fibronectin coated plate. At 70~80% confluence, the MSCs were harvested and cultured in MCM supplemented with Activin A, at a 50 ng/mL concentration, and FGF4. The expression of the genes related with MSCs or primitive endoderm were analyzed by RT-PCR. The changes of cell morphology for differentiation were also observed by a light microscope & a SEM. Results: The expression of genes related with primitive foregut endoderm was seen in the groups that were treated with a higher concentration of Activin A. The morphology of the cells that differentiated into definitive endoderm were not different from those of the undifferentiated MSCs. The expression of genes related with functional primitive hepatocytes was seen in the early phase during hepatic differentiation. The cell morphology was changed to a similar cuboidal form in a time-dependent manner. Conclusion: Activin A promotes a more rapid induction of definitive endoderm. It also makes an efficient condition for the differentiation into primitive foregut endoderm at a higher concentration.

키워드

참고문헌

  1. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004;36:568-584. https://doi.org/10.1016/j.biocel.2003.11.001
  2. Kume S. Stem-cell-based approaches for regenerative medicine. Dev Growth Differ 2005;47:393-402. https://doi.org/10.1111/j.1440-169X.2005.00814.x
  3. Denker HW. Potentiality of embryonic stem cells: an ethical problem even with alternative stem cell sources. J Med Ethics 2006;32:665-871. https://doi.org/10.1136/jme.2005.014738
  4. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-676. https://doi.org/10.1016/j.cell.2006.07.024
  5. Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 2009;27: 743-745. https://doi.org/10.1038/nbt.1554
  6. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 2008;11:343-353.
  7. Sakaida I. Clinical application of bone marrow cell transplantation for liver diseases. J Gastroenterol 2006;41:93-94. https://doi.org/10.1007/s00535-006-1746-9
  8. Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 2005;328:258-264. https://doi.org/10.1016/j.bbrc.2004.12.158
  9. Taléns-Visconti R, Bonora A, Jover R, et al. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 2006;12:5834-5845. https://doi.org/10.3748/wjg.v12.i36.5834
  10. Parashurama N, Nahmias Y, Cho CH, et al. Activin alters the kinetics of endoderm induction in embryonic stem cells cultured on collagen gels. Stem Cells 2008;26:474-484. https://doi.org/10.1634/stemcells.2007-0303
  11. Hay DC, Zhao D, Fletcher J, et al. Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells 2008;26:894-902. https://doi.org/10.1634/stemcells.2007-0718
  12. Zorn AM, Wells JM. Molecular basis of vertebrate endoderm development. Int Rev Cytol 2007;259:49-111. https://doi.org/10.1016/S0074-7696(06)59002-3
  13. Banas A, Teratani T, Yamamoto Y, et al. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol 2009;24:70-77. https://doi.org/10.1111/j.1440-1746.2008.05496.x
  14. Böttcher RT, Niehrs C. Fibroblast growth factor signaling during early vertebrate development. Endocr Rev 2005;26: 63-77. https://doi.org/10.1210/er.2003-0040
  15. Pevsner-Fisher M, Zipori D. Environmental signals regulating mesenchymal progenitor cell growth and differentiation. In : Rajasekhar VK, Vemuri MC, editors. Regulatory networks in stem cells. Humana Press 2009;175-184.
  16. Gerson SL. Mesenchymal stem cells: no longer second class marrow citizens. Nat Med 1999;5:262-264. https://doi.org/10.1038/6470
  17. Choi FJ, Kwon JY, Kim Ho, Kim SH, Choi YJ, Cho JA. et al. The characterization of the mesenchymal stem cells derived from fat, cord blood, placenta tissues. Korean HBP Surg 2006;10:1-6.
  18. Strem BM, Hicok KC, Zhu M, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 2005; 54:132-141. https://doi.org/10.2302/kjm.54.132
  19. Xu RH, Sampsell-Barron TL, Gu F, et al. NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell 2008;3:196-206. https://doi.org/10.1016/j.stem.2008.07.001
  20. Banas A, Teratani T, Yamamoto Y, et al. Adipose tissuederived mesenchymal stem cells as a source of human hepatocytes. Hepatology 2007;46:219-228. https://doi.org/10.1002/hep.21704
  21. Watabe T, Miyazono K. Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res 2009;19: 103-115. https://doi.org/10.1038/cr.2008.323
  22. McLean AB, D'Amour KA, Jones KL, et al. Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells 2007;25:29-38. https://doi.org/10.1634/stemcells.2006-0219
  23. Kroon E, Martinson LA, Kadoya K, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008;26:443-452. https://doi.org/10.1038/nbt1393
  24. D'Amour KA, Bang AG, Eliazer S, et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006;24:1392-1401. https://doi.org/10.1038/nbt1259
  25. Kim SK, Hebrok M, Li E, et al. Activin receptor patterning of foregut organogenesis. Genes Dev 2000;14:1866-1871.
  26. Clotman F, Lemaigre FP. Control of hepatic differentiation by activin/TGFbeta signaling. Cell Cycle 2006;5:168-171. https://doi.org/10.4161/cc.5.2.2341
  27. Guo X, Wang XF. Signaling cross-talk between TGF-beta/ BMP and other pathways. Cell Res 2009;19:71-88. https://doi.org/10.1038/cr.2008.302
  28. Vallier L, Alexander M, Pedersen RA. Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells. J Cell Sci 2005;118:4495-4509. https://doi.org/10.1242/jcs.02553
  29. Shiraki N, Umeda K, Sakashita N, Takeya M, Kume K, Kume S. Differentiation of mouse and human embryonic stem cells into hepatic lineages. Genes Cells 2008;13:731-746. https://doi.org/10.1111/j.1365-2443.2008.01201.x
  30. Watt AJ, Garrison WD, Duncan SA. HNF4: a central regulator of hepatocyte differentiation and function. Hepatology 2003; 37:1249-1253. https://doi.org/10.1053/jhep.2003.50273