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What is the real contribution of extrahepatic cells to liver regeneration?

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Abstract

Extrahepatic cells, especially bone marrow (BM) cells, might contribute to liver repair, but recent published evidence suggests that they do not play a role in the normally regenerating liver. The mechanism by which extrahepatic cells express a liver-specific function in the liver, whether by transdifferentiation or by cell fusion, remains unclear. In this review, we investigate the status of findings on this controversial subject and summarize the recent research.

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References

  1. Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000;31: 235–240.

    Article  PubMed  CAS  Google Scholar 

  2. Baccarani U, Donini A, Risaliti A, Bresadola F. Replacement of liver venous endothelium. Lancet 2001;357:2137.

    Article  PubMed  CAS  Google Scholar 

  3. Körbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Eng J Med 2002;346:738–746.

    Article  Google Scholar 

  4. Fujii H, Hirose T, Oe S, Yasuchika K, Azuma H, Fujikawa T, et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol 2002;36:653–659.

    Article  PubMed  CAS  Google Scholar 

  5. Ferry N, Hadchouel M. Liver regeneration: with a little help from marrow. J Hepatol 2002;36:695–697.

    Article  PubMed  Google Scholar 

  6. Terai S, Sakaida I, Nishina H, Okita K. Lesson from the GFP/CCl4 model-translational research project: the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis. J Hepatobiliary Pancreat Surg 2005;12:203–207.

    Article  PubMed  Google Scholar 

  7. Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology 2004;78;83–88.

    Google Scholar 

  8. am Esch JS 2nd, Knoefel WT, Klein M, Ghodsizad A, Fuerst G, Poll LW, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells 2005;23:463–470.

    Article  PubMed  Google Scholar 

  9. Conzelmann LO, Hines IN, Kremer M, Perry AW, Lemasters JJ, Wheeler MD. Extrahepatic cells contribute to the progenitor/ stem cell response following reduced-size liver transplantation in mice. Exp Biol Med (Maywood). 2007;232:571–580.

    CAS  Google Scholar 

  10. Dahlke MH, Popp FC, Bahlmann FH, Aselmann H, Jäger MD, Neipp M, et al. Liver regeneration in a retrorsine/CCl4-induced acute liver failure model: do bone marrow-derived cells contribute? J Hepatol 2003;39:365–373.

    Article  PubMed  CAS  Google Scholar 

  11. Hunter Best D, Coleman WB. Cells of origin of small hepatocytelike progenitor cells in the retrorsine model of rat liver injury and regeneration. J Hepatol 2008;48:369–371.

    Article  PubMed  CAS  Google Scholar 

  12. Di Campli C, Piscaglia AC, Giuliante F, Rutella S, Bonanno G, Zocco MA, et al. No evidence of hematopoietic stem cell mobilization in patients submitted to hepatectomy or in patients with acute on chronic liver failure. Transplant Proc 2005;37:2563–2566.

    Article  PubMed  Google Scholar 

  13. Moritoki Y, Ueno Y, Kanno N, Yamagiwa Y, Fukushima K, Gershwin ME, et al. Lack of evidence that bone marrow cells contribute to cholangiocyte repopulation during experimental cholestatic ductal hyperplasia. Liver Int 2006;26:457–466.

    Article  PubMed  Google Scholar 

  14. Tomiyama K, Miyazaki M, Nukui M, Takaishi M, Nakao A, Shimizu N, et al. Contribution of cells of intact extrahepatic tissue origin to hepatocyte regeneration in transplanted rat liver. Transplantation 2007;83:624–630.

    Article  PubMed  Google Scholar 

  15. Popp FC, Slowik P, Eggenhofer E, Renner P, Lang SA, Stoeltzing O, et al. No contribution of multipotent mesenchymal stromal cells to liver regeneration in a rat model of prolonged hepatic injury. Stem Cells. 2007;25:639–645.

    Article  PubMed  CAS  Google Scholar 

  16. Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, et al. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 2006;24:2292–2298.

    Article  PubMed  CAS  Google Scholar 

  17. Eguchi S, Kamlot A, Ljubimova J, Lebow LT, Demetriou AA, Rozga J. A novel experimental animal model of fulminant hepatic failure. Survival and effect on biochemistry and liver regeneration. Hepatology 1996:24;1452-1459.

    Google Scholar 

  18. Eguchi S, Yanaga K, Sugiyama N, Okudaira S, Furui J, Kanematsu T. Changes in serum levels of hepatocyte growth factor in patients undergoing adult-to-adult living donor liver transplantation. Transplantation 2003:76;1769–1770.

    Article  PubMed  CAS  Google Scholar 

  19. Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, et al. Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells 2006;24:1822–1830.

    Article  PubMed  Google Scholar 

  20. Cantz T, Sharma AD, Jochheim-Richter A, Arseniev L, Klein C, Manns MP, et al. Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration. Cell Transplant 2004;13: 659–666.

    Article  PubMed  Google Scholar 

  21. Beaudry P, Hida Y, Udagawa T, Alwayn IP, Greene AK, Arsenault D, et al. Endothelial progenitor cells contribute to accelerated liver regeneration. J Pediatr Surg 2007;42:1190–1198.

    Article  PubMed  Google Scholar 

  22. Lai HS, Chen Y, Lin WH, Chen CN, Wu HC, Chang CJ, et al. Quantitative gene expression analysis by cDNA microarray during liver regeneration after partial hepatectomy in rats. Surg Today 2005;35:396–403.

    Article  PubMed  CAS  Google Scholar 

  23. Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004;40;1275–1284.

    Article  PubMed  CAS  Google Scholar 

  24. Brulport M, Schormann W, Bauer A, Hermes M, Elsner C, Hammersen FJ, et al. Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers. Hepatology 2007;46:861–870.

    Article  PubMed  Google Scholar 

  25. Wu T, Cieply K, Nalesnik MA, Randhawa PS, Randhawa PS, Sonzogni A, et al. Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts. Am J Transplant 2003;3:1173–1181.

    Article  PubMed  Google Scholar 

  26. Camargo FD, Finegold M, Goodell MA. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J Clin Invest 2004;113:1266–1270.

    PubMed  CAS  Google Scholar 

  27. Willenbring H, Bailey AS, Foster M, Foster M, Akkari Y, Dorrell C, et al. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat Med 2004;10:744–748.

    Article  PubMed  CAS  Google Scholar 

  28. Quintana-Bustamante O, Alvarez-Barrientos A, Kofman AV, Fabregat I, Bueren JA, Theise ND, et al. Hematopoietic mobilization in mice increases the presence of bone marrow-derived hepatocytes via in vivo cell fusion. Hepatology 2006;43:108–116.

    Article  PubMed  Google Scholar 

  29. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003;422:901–904.

    Article  PubMed  CAS  Google Scholar 

  30. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003;422:897–901.

    Article  PubMed  CAS  Google Scholar 

  31. Kawashita Y, Guha C, Yamanouchi K, Ito Y, Kamohara Y, Kanematsu T. Liver repopulation: A new concept of hepatocyte transplantation. Surg Today 2005;35:705–710.

    Article  PubMed  Google Scholar 

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Eguchi, S., Kanematsu, T. What is the real contribution of extrahepatic cells to liver regeneration?. Surg Today 39, 1–4 (2009). https://doi.org/10.1007/s00595-008-3836-1

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  • DOI: https://doi.org/10.1007/s00595-008-3836-1

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