Human bone marrow mesenchymal stem cell-derived hepatocytes improve the mouse liver after acute acetaminophen intoxication by preventing progress of injury

International Journal of Molecular Sciences

Volumn 15, Issue 4, 2014, Pages 7004-7028

  Stock, Peggy ^a   Brückner, Sandra ^a   Winkler, Sandra ^a   Dollinger, Matthias M ^b   Christ, Bruno ^a  

^a UNIVERSITY HOSPITAL LEIPZIG   (Germany)

^b UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

Acute liver injury; Cell transplantation; Hepatocyte differentiation; Human mesenchymal stem cells; Stem cell derived hepatocytes

Indexed keywords

ALBUMIN; ASPARTATE AMINOTRANSFERASE; CYTOCHROME P450 1A; CYTOCHROME P450 2B; FERRITIN; GLUTAMATE AMMONIA LIGASE; PHOSPHOENOLPYRUVATE CARBOXYKINASE (PYROPHOSPHATE); DNA BINDING PROTEIN; PARACETAMOL; RAG2 PROTEIN, MOUSE;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG INTOXICATION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; LIVER CELL DAMAGE; MALE; MOUSE; NONHUMAN; STEM CELL TRANSPLANTATION; TISSUE DISTRIBUTION; TISSUE REPAIR; WESTERN BLOTTING; ANIMAL; BLOOD; BONE MARROW CELL; CELL DIFFERENTIATION; CYTOLOGY; DRUG-INDUCED LIVER INJURY; GENETICS; LIVER CELL; LIVER REGENERATION; MESENCHYMAL STROMA CELL; METABOLISM; TIME; TOXICITY; TRANSPLANTATION;

ACETAMINOPHEN; ANIMALS; ASPARTATE AMINOTRANSFERASES; BONE MARROW CELLS; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; DRUG-INDUCED LIVER INJURY; HEPATOCYTES; HUMANS; LIVER REGENERATION; MALE; MESENCHYMAL STROMAL CELLS; MICE; TIME FACTORS;

EID: 84899133542     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms15047004     Document Type: Article

References (73)

1. Alison, M.R.; Vig, P.; Russo, F.; Bigger, B.W.; Amofah, E.; Themis, M.; Forbes, S. Hepatic stem cells: From inside and outside the liver? Cell Prolif. 2004, 37, 1-21.
2. Fausto, N. Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells. Hepatology 2004, 39, 1477-1487.
3. Russo, F.P.; Kallis, Y.N.; Alison, M.R.; Forbes, S.J. Bone marrow cells in the liver: Diverse cells, diverse effects. Hepatology 2007, 46, 604-605.
4. Grompe, M. The role of bone marrow stem cells in liver regeneration. Semin. Liver Dis. 2003, 23, 363-372.
5. Kallis, Y.N.; Alison, M.R.; Forbes, S.J. Bone marrow stem cells and liver disease. Gut 2007, 56, 716-724.
6. Oertel, M.; Shafritz, D.A. Stem cells, cell transplantation and liver repopulation. Biochim. Biophys. Acta 2008, 1782, 61-74.
7. Fox, I.J.; Strom, S.C. To be or not to be: Generation of hepatocytes from cells outside the liver. Gastroenterology 2008, 134, 878-881.
8. Willenbring, H.; Bailey, A.S.; Foster, M.; Akkari, Y.; Dorrell, C.; Olson, S.; Finegold, M.; Fleming, W.H.; Grompe, M. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat. Med. 2004, 10, 744-748.
9. Wang, X.; Willenbring, H.; Akkari, Y.; Torimaru, Y.; Foster, M.; Al-Dhalimy, M.; Lagasse, E.; Finegold, M.; Olson, S.; Grompe, M. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003, 422, 897-901.
10. Bunnell, B.A.; Deng, W.; Robinson, C.M.; Waldron, P.R.; Bivalacqua, T.J.; Baber, S.R.; Hyman, A.L.; Kadowitz, P.J. Potential application for mesenchymal stem cells in the treatment of cardiovascular diseases. Can. J. Physiol. Pharmacol. 2005, 83, 529-539.
11. Christopeit, M.; Schendel, M.; Foll, J.; Muller, L.P.; Keysser, G.; Behre, G. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia 2008, 22, 1062-1064.
12. Ohnishi, S.; Nagaya, N. Prepare cells to repair the heart: Mesenchymal stem cells for the treatment of heart failure. Am. J. Nephrol. 2007, 27, 301-307.
13. Ringdén, O.; Uzunel, M.; Rasmusson, I.; Remberger, M.; Sundberg, B.; Lönnies, H.; Marschall, H.-U.; Dlugosz, A.; Szakos, A.; Hassan, Z. et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006, 81, 1390-1397.
14. Christ, B.; Dollinger, M.M. The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver. Curr. Opin. Org. Transplant. 2011, 16, 69-75.
15. Chamberlain, G.; Fox, J.; Ashton, B.; Middleton, J. Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007, 25, 2739-2749.
16. Krampera, M.; Pasini, A.; Pizzolo, G.; Cosmi, L.; Romagnani, S.; Annunziato, F. Regenerative and immunomodulatory potential of mesenchymal stem cells. Curr. Opin. Pharmacol. 2006, 6, 435-441.
17. Le Blanc, K.; Ringden, O. Immunomodulation by mesenchymal stem cells and clinical experience. J. Intern. Med. 2007, 262, 509-525.
18. Lysy, P.A.; Campard, D.; Smets, F.; Malaise, J.; Mourad, M.; Najimi, M.; Sokal, E.M. Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells. Cell Prolif. 2008, 41, 36-58.
19. Lee, K.D.; Kuo, T.K.; Whang-Peng, J.; Chung, Y.F.; Lin, C.T.; Chou, S.H.; Chen, J.R.; Chen, Y.P.; Lee, O.K. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004, 40, 1275-1284.
20. Aurich, I.; Mueller, L.P.; Aurich, H.; Luetzkendorf, J.; Tisljar, K.; Dollinger, M.M.; Schormann, W.; Walldorf, J.; Hengstler, J.G.; Fleig, W.E. et al. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 2007, 56, 405-415.
21. Oyagi, S.; Hirose, M.; Kojima, M.; Okuyama, M.; Kawase, M.; Nakamura, T.; Ohgushi, H.; Yagi, K. Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J. Hepatol. 2006, 44, 742-748.
22. Banas, A.; Teratani, T.; Yamamoto, Y.; Tokuhara, M.; Takeshita, F.; Quinn, G.; Okochi, H.; Ochiya, T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 2007, 46, 219-228.
23. Kuo, T.K.; Hung, S.-P.; Chuang, C.-H.; Chen, C.-T.; Shih, Y.-R.V.; Fang, S.-C.Y.; Yang, V.W.; Lee, O.K. Stem cell therapy for liver disease: Parameters Governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 2008, 134, 2111-2121.
24. Banas, A.; Teratani, T.; Yamamoto, Y.; Tokuhara, M.; Takeshita, F.; Osaki, M.; Kawamata, M.; Kato, T.; Okochi, H.; Ochiya, T. IFATS series: In vivo therapeutic potential of human adipose tissue mesenchymal stem cells (at-mscs) after transplantation into mice with liver injury. Stem Cells 2008, 26, 2705-2712.
25. Parekkadan, B.; van Poll, D.; Suganuma, K.; Carter, E.A.; Berthiaume, F.; Tilles, A.W.; Yarmush, M.L. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One 2007, 2, e941.
26. Van Poll, D.; Parekkadan, B.; Cho, C.H.; Berthiaume, F.; Nahmias, Y.; Tilles, A.W.; Yarmush, M.L. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 2008, 47, 1634-1643.
27. Sgodda, M.; Aurich, H.; Kleist, S.; Aurich, I.; Konig, S.; Dollinger, M.M.; Fleig, W.E.; Christ, B. Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp. Cell Res. 2007, 313, 2875-2886.
28. Stock, P.; Staege, M.S.; Müller, L.P.; Sgodda, M.; Völker, A.; Volkmer, I.; Lützkendorf, J.; Christ, B. Hepatocytes derived from adult stem cells. Transplant. Proc. 2008, 40, 620-623.
29. Christ, B.; Pelz, S. Implication of hepatic stem cells in functional liver repopulation. Cytometry A 2013, 8, 90-102.
30. Hughes, R.D.; Mitry, R.R.; Dhawan, A. Current status of hepatocyte transplantation. Transplantation 2012, 93, 342-347.
31. O'Grady, J.G. Acute liver failure. Postgrad. Med. J. 2005, 81, 148-154.
32. Lee, W.M. Acetaminophen and the U.S. acute liver failure study group: Lowering the risks of hepatic failure. Hepatology 2004, 40, 6-9.
33. James, L.P.; Mayeux, P.R.; Hinson, J.A. Acetaminphen-induced hepatotoxicity. Drug Metab. Dispos. 2003, 31, 1499-1506.
34. Jaeschke, H.; Bajt, M.L. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol. Sci. 2006, 89, 31-41.
35. Mehendale, H.M. Tissue repair: An important determinant of final outcome of toxicant-induced injury. Toxicol. Pathol. 2005, 33, 41-51.
36. Lee, V.M.; Cameron, R.G.; Archer, M.C. Zonal location of compensatory hepatocyte proliferation following chemically induced hepatotoxicity in rats and humans. Toxicol. Pathol. 1998, 26, 621-627.
37. Kofman, A.V.; Morgan, G.; Kirschenbaum, A.; Osbeck, J.; Hussain, M.; Swenson, S.; Theise, N.D. Dose- and time-dependent oval cell reaction in acetaminophen-induced murine liver injury. Hepatology 2005, 41, 1252-1261.
38. Fisher, R.A.; Strom, S.C. Human hepatocyte transplantation. Transplantation 2006, 82, 441-449.
39. Smets, F.; Najimi, M.; Sokal, E.M. Cell transplantation in the treatment of liver diseases. Pediatr. Transplant. 2008, 12, 6-13.
40. Francois, S.; Mouiseddine, M.; Allenet-Lepage, B.; Voswinkel, J.; Douay, L.; Benderitter, M.; Chapel, A. Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation, and trophic effects. BioMed Res. Int. 2013, 2013, 151679.
41. Stock, P.; Brueckner, S.; Ebensing, S.; Hempel, M.; Dollinger, M.M.; Christ, B. The generation of hepatocytes from mesenchymal stem cells and engraftment into murine liver. Nat. Protoc. 2010, 5, 617-627.
42. Kallis, Y.N.; Forbes, S.J. The bone marrow and liver fibrosis: Friend or foe? Gastroenterology 2009, 137, 1218-1221.
43. Mitchell, J.R.; Jollow, D.J.; Potter, W.Z.; Gillette, J.R.; Brodie, B.B. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Therap. 1973, 187, 211-217.
44. Jollow D.J.; Thorgeirsson, S.S.; Potter, W.Z.; Hashimoto, M.; Mitchell, J.R. Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology 1974, 12, 251-271.
45. Jaeschke, H.; Gores, G.J.; Cederbaum, A.I.; Hinson, J.A.; Pessayre, D.; Lemasters, J.J. Mechanisms of hepatotoxicity. Toxicol. Sci. 2002, 65, 166-176.
46. Doi, K.; Ishida, K. Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced hepatotoxicity and nephrotoxicity in rats and mice. J. Toxicol. Sci. 2009, 34, 1-11.
47. Christ, B.; Brückner, S. Rodent animal models for surrogate analysis of cell therapy in acute liver failure. Front. Physiol. 2012, 3, 78.
48. Ni, H.-M.; Williams, J.A.; Jaeschke, H.; Ding, W.-X. Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver. Redox Biol. 2013, 1, 427-432.
49. Blazka, M.E.; Wilmer, J.L.; Holladay, S.D.; Wilson, R.E.; Luster, M.I. Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol. 1995, 133, 43-52.
50. Bourdi, M; Masubuchi, Y.; Reilly, T.P.; Amouzadeh, H.R.; Martin, J.L.; George, J.W.; Shah, A.G.; Pohl, L.R. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase. Hepatology 2002, 35, 289-298.
51. Gardner, C.R.; Laskin, J.D.; Dambach, D.M.; Chiu, H.; Durham, S.K.; Zhou, P.; Bruno, M.; Gerecke, D.R.; Gordon, M.K.; Laskin, D.L. Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1: Potential role of inflammatory mediators. Toxicol. Appl. Pharmacol. 2003, 192, 119-130.
52. Götherström, C. Immunomodulation by multipotent mesenchymal stromal cells. Transplantation 2007, 84, S35-S37.
53. Aurich, H.; Sgodda, M.; Kaltwasser, P.; Vetter, M.; Weise, A.; Liehr, T.; Brulport, M.; Hengstler, J.G.; Dollinger, M.M.; Fleig, W.E. et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 2009, 58, 570-581.
54. Xie, J.; Wang, W.; Si, J.-W.; Miao, X.-Y.; Li, J.-C.; Wang, Y.-C.; Wang, Z.-R.; Ma, J.; Zhao, X.-C.; Li, Z. et al. Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells. Cell. Immunol. 2013, 281, 68-75.
55. Huang, C.-K.; Lee, S.O.; Lai, K.-P.; Ma, W.-L.; Lin, T.-H.; Tsai, M.-Y.; Luo, J.; Chang, C. Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis. Hepatology 2013, 57, 1550-1563.
56. Zagoura, D.S.; Roubelakis, M.G.; Bitsika, V.; Trohatou, O.; Pappa, K.I.; Kapelouzou, A.; Antsaklis, A.; Anagnou, N.P. Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure. Gut 2012, 61, 894-906.
57. Salomone, F.; Barbagallo, I.; Puzzo, L.; Piazza, C.; Li Volti, G. Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with acetaminophen liver injury. Stem Cell Res. 2013, 11, 1037-1044.
58. Koenig, S.; Aurich, H.; Schneider, C.; Krause, P.; Haftendorn, R.; Becker, H.; Christ, B. Zonal expression of hepatocytic marker enzymes during liver repopulation. Histochem. Cell Biol. 2007, 128, 105-114.
59. Aurich, H.; Koenig, S.; Schneider, C.; Walldorf, J.; Krause, P.; Fleig, W.E.; Christ, B. Functional characterization of serum-free cultured rat hepatocytes for downstream transplantation applications. Cell Transplant. 2005, 14, 497-506.
60. Butler, S.L.; Dong, H.; Cardona, D.; Jia, M.; Zheng, R.; Zhu, H.; Crawford, J.M.; Liu, C. The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase1. Lab. Investig. 2007, 88, 78-88.
61. Sato, Y.; Araki, H.; Kato, J.; Nakamura, K.; Kawano, Y.; Kobune, M.; Sato, T.; Miyanishi, K.; Takayama, T.; Takahashi, M. et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 2005, 106, 756-763.
62. Seo, M.J.; Suh, S.Y.; Bae, Y.C.; Jung, J.S. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem. Biophys. Res. Commun. 2005, 328, 258-264.
63. Yukawa, H.; Noguchi, H.; Oishi, K.; Takagi, S.; Hamaguchi, M.; Hamajima, N.; Hayashi, S. Cell transplantation of adipose tissue-derived stem cells in combination with heparin attenuated acute liver failure in mice. Cell Transplant. 2009, 18, 611-618.
64. Yagi, H.; Soto-Gutierrez, A.; Kitagawa, Y.; Tilles, A.W.; Tompkins, R.G.; Yarmush, M.L. Bone marrow mesenchymal stromal cells attenuate organ injury induced by lps and burn. Cell Transplant. 2010, 19, 823-830.
65. Chen, Y.; Xiang, L.-X.; Shao, J.-Z.; Pan, R.-L.; Wang, Y.-X.; Dong, X.-J.; Zhang, G.-R. Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver. J. Cell. Mol. Med. 2010, 14, 1494-1508.
66. Jin, S.Z.; Meng, X.W.; Han, M.Z.; Sun, X.; Sun, L.Y.; Liu, B.R. Stromal cell derived factor-1 enhances bone marrow mononuclear cell migration in mice with acute liver failule. World J. Gastroenterol. 2009, 15, 2657-2664.
67. Collino, F.; Deregibus, M.C.; Bruno, S.; Sterpone, L.; Aghemo, G.; Viltono, L.; Tetta, C.; Camussi, G. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of mirnas. PLoS One 2010, 5, e11803.
68. Deregibus, M.C.; Tetta, C.; Camussi, G. The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information. Histol. Histopathol. 2010, 25, 397-404.
69. Williams, C.D.; Bajt, M.L.; Sharpe, M.R.; McGill, M.R.; Farhood, A.; Jaeschke, H. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans. Toxicol. Appl. Pharmacol. 2014, 275, 122-133.
70. Liu, Z.-X.; Kaplowitz, N. Role of innate immunity in acetaminophen-induced hepatotoxicity. Expert Opin. Drug Metab. Toxicol. 2006, 2, 493-503.
71. Jaeschke, H.; Williams, C.D.; Ramachandran, A.; Bajt, M.L. Acetaminophen hepatotoxicity and repair: The role of sterile inflammation and innate immunity. Liver Int. 2012, 32, 8-20.
72. Walldorf, J.; Hillebrand, C.; Aurich, H.; Stock, P.; Hempel, M.; Ebensing, S.; Fleig, W.E.; Seufferlein, T.; Dollinger, M.M.; Christ, B. Propranolol impairs liver regeneration after partial hepatectomy in C57Bl/6-mice by transient attenuation of hepatic lipid accumulation and increased apoptosis. Scand. J. Gastroenterol. 2010, 45, 468-476.
73. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.