The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver

Current Opinion in Organ Transplantation

Volumn 16, Issue 1, 2011, Pages 69-75

  Christ, Bruno ^a,b   Dollinger, Matthias M ^a,b  

^a UNIVERSITY OF LEIPZIG   (Germany)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

cell therapy; hepatocyte differentiation; liver diseases; mesenchymal stem cells

Indexed keywords

APOPTOSIS; ARTICLE; BONE MARROW; CELL DIFFERENTIATION; CELL MIGRATION; CELLULAR IMMUNITY; HEPATOCYTE TRANSPLANTATION; HOST; HUMAN; HUMORAL IMMUNITY; IMMUNOGENICITY; IMMUNOMODULATION; INFLAMMATION; LIVER CELL; LIVER REGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; RECIPIENT; TISSUE REPAIR;

ANIMALS; CELL DIFFERENTIATION; HEPATOCYTES; HUMANS; LIVER; LIVER REGENERATION; LIVER TRANSPLANTATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS;

EID: 78751614801     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e3283424f5b     Document Type: Article

References (103)

1. Nussler A, Konig S, Ott M, et al. Present status and perspectives of cellbased therapies for liver diseases. J Hepatol 2006; 45:144-159.
2. Smets F, Najimi M, Sokal EM. Cell transplantation in the treatment of liver diseases. Pediatric Transplant 2008; 12:6-13.
3. Enns GM, Millan MT. Cell-based therapies for metabolic liver disease. Molec Genet Metab 2008; 95:3-10.
4. Meyburg J, Das AM, Hoerster F, et al. One liver for four children: first clinical series of liver cell transplantation for severe neonatal urea cycle defects. Transplantation 2009; 87:636-641.
5. Dhawan A, Puppi J, Hughes RD, Mitry RR. Human hepatocyte transplantation: current experience and future challenges. Nat Rev Gastroenterol Hepatol 2010; 7:288-298.
6. Lange C, Bassler P, Lioznov MV, et al. Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplant Proc 2005; 37:276-279. (Pubitemid 40459760)
7. Sgodda M, Aurich H, Kleist S, et al. Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp Cell Res 2007; 313:2875-2886.
8. Aurich H, Sgodda M, Kaltwaer P, et al. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 2009; 58:570-581.
9. Aurich I, Mueller LP, Aurich H, et al. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 2007; 56:405-415.
10. Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 2002; 109:1291-1302. (Pubitemid 34546893)
11. Talens-Visconti R, Bonora A, Jover R, et al. Human mesenchymal stem cells from adipose tissue: differentiation into hepatic lineage. Toxicol in Vitro 2007; 21:324-329.
12. 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.
13. Lee KD, Kuo TK, Whang-Peng J, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004; 40:1275-1284.
14. Hong SH, Gang EJ, Jeong JA, et al. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun 2005; 330:1153-1161.
15. Banas A, Teratani T, Yamamoto Y, et al. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 2007; 46:219-228.
16. Wang PP, Wang JH, Yan ZP, et al. Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction. Biochem Biophys Res Commun 2004; 320:712-716.
17. Stock P, Bruckner S, Ebensing S, et al. The generation of hepatocytes from mesenchymal stem cells and engraftment into murine liver. Nat Protoc 2010; 5:617-627.
18. Stock P, Staege MS, Mü ller LP, et al. Hepatocytes derived from adult stem cells. Transplant Proc 2008; 40:620-623.
19. Talens-Visconti R, Bonora A, Jover R, et al. Human mesenchymal stem cells from adipose tissue: differentiation into hepatic lineage. Toxicology in vitro. In vitro cytotoxicity mechanisms. Proceedings of the 46th ETCS International Meeting and the 3rd International Joint Meeting of AICC and CELLTOX 2007; 21:324-329.
20. Schä fer R, Dominici M, Mü ller I, et al. Basic research and clinical applications of nonhematopoietic stem cells. Cytotherapy; 2009; 11: 245-255.
21. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-317.
22. Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005; 33:1402-1416.
23. 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
24. Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006; 99.
25. Chateauvieux S, Ichante J-L, Delorme B, et al. The molecular profile of mouse stromal mesenchymal stem cells. Physiol Genomics 2007; 29:128-138.
26. Snykers S, De Kock J, Rogiers V, Vanhaecke T. In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 2009; 27:577-605.
27. Zaret KS. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. 2008; 9:329-340.
28. Huppert SS, Magnuson MA. New complexity in differentiating stem cells toward hepatic and pancreatic fates. Sci Signal 2009; 2:pe50.
29. Stock P, Staege MS, Mü ller LP, et al. Hepatocytes derived from adult stem cells. Transplant Proc 2008; 40:620-623.
30. Yamamoto Y, Banas A, Murata S, et al. A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells. FEBS J 2008; 275:1260-1273.
31. Hay DC, Fletcher J, Payne C, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci 2008; 105:12301-12306.
32. Fletcher J, Cui W, Samuel K, et al. The inhibitory role of stromal cell mesenchyme on human embryonic stem cell hepatocyte differentiation is overcome by Wnt3a treatment. Cloning Stem Cells 2008; 10:331-340.
33. Ke Z, Zhou F, Wang L, et al. Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes. Biochem Biophys Res Commun 2008; 367:342-348.
34. Yoshida Y, Shimomura T, Sakabe T, et al. A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells. Am J Physiol Gastrointest Liver Physiol 2007; 293:G1089-G1098].
35. Sato N, Meijer L, Skaltsounis L, et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. 2004; 10:55-63.]
36. Sgodda M, Christ B. Impact of -catenin on hepatocyte differentiation of human adipose tissue-derived mesenchymal stem cells (MSC). Cytometry PtA 2009; 75A:713-714].
37. Burke ZD, Reed KR, Phesse TJ, et al. Liver zonation occurs through a -catenin-dependent, c-Myc-independent mechanism. Gastroenterology 2009; 136:2316-2324; e2313].
38. Gebhardt R, Baldysiak-Figiela A, Krügela V, et al. Hepatocellular expression of glutamine synthetase: an indicator of morphogen actions as master regulators of zonation in adult liver. Prog Histochem Cytochem 2007; 41:201-266].
39. Sekine S, Yu-Ang Lan B, Bedolli M, et al. Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice. Hepatology 2006; 43:817-825.
40. Colletti M, Cicchini C, Conigliaro A, et al. Convergence of Wnt signaling on the HNF4alpha-driven transcription in controlling liver zonation. Gastroenterology 2009; 137:660-672.
41. Benhamouche S, Decaens T, Godard C, et al. Apc tumor suppressor gene is the zonation-keeper of mouse liver. Develop Cell 2006; 10:759-770.
42. Rajvanshi P, Kerr A, Bhargava KK, et al. Studies on liver repopulation using the dipeptidyl peptidase IV-deficient rat and other rodent recipients: cell size and structure relationships regulate capacity for increased transplanted hepatocyte mass in the liver lobule. Hepatology 1996; 23:482-496.
43. Ponder KP, Gupta S, Leland F, et al. Mouse hepatocytes migrate to the liver parenchyma and function indefinitely after intrasplenic transplantation. Proc Natl Acad Sci USA 1991; 88:1217-1221.
44. Gupta S, Rajvanshi P, Sokhi R, et al. Entry and migration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium. Hepatology 1999; 29:509-519.
45. Slehria S, Rajvanshi P, Ito Y, et al. Hepatic sinusoidal vasodilatators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver. Hepatology 2002; 35:1320-1328. (Pubitemid 34966886)
46. Gupta S, Rajvanshi P, Aragona E, et al. Transplanted hepatocytes proliferate differently after CCl4 treatment and hepatocyte growth factor infusion. Am J Physiol 1999; 276:G629-638.
47. Laconi E, Oren R, Mukhopadhyay DK, et al. Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 1998; 153:319-329.
48. Gupta S, Aragona E, Vemuru RP, et al. Permanent engraftment and function of hepatocytes delivered to the liver: implications for gene therapy and liver regeneration. Hepatology 1991; 14:144-149.
49. Oertel M, Shafritz DA. Stem cells, cell transplantation and liver repopulation. Biochim Biophys Acta Molec Basis Dis 2008; 1782:61-74.
50. Strom SC, Bruzzone P, Cai H, et al. Hepatocyte transplantation: clinical experience and potential for future use. Cell Transplant 2006; 15 (Suppl 1): S105-110.
51. Horslen SP, Fox IJ. Hepatocyte transplantation. Transplantation 2004; 77:1481-1486.
52. Seppen J, Filali EE, Elferink RO. Small animal models of hepatocyte transplantation. Methods Mol Biol 2009; 481:75-82.
53. Weber A, Groyer-Picard M-T, Franco D, Dagher I. Hepatocyte transplantation in animal models. Liver Transplant 2009; 15:7-14.
54. Laconi S, Pillai S, Paolo Porcu P, et al. Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine. Am J Pathol 2001; 158:771-777.
55. Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 2005; 106:756-763.
56. Vilalta M, Dégano IR, Bagó J, et al. Biodistribution, long-term survival, and safety of human adipose tissue-derived mesenchymal stem cells transplanted in nude mice by high sensitivity noninvasive bioluminescence imaging. Stem Cells Develop 2008; 17:993-1004.
57. Sancho-Bru P, Najimi M, Caruso M, et al. Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside? Gut 2009; 58:594-603.
58. Parekkadan B, van Poll D, Megeed Z, et al. Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun 2007; 363:247-252. This study demonstrated that not the differentiation of MSC into hepatocytes was the mode of action but paracrine secretion of factors rescuing the injured liver from end-stage damage.
59. van Poll D, Parekkadan B, Cho CH, et al. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 2008; 47:1634-1643. This study demonstrated that not the differentiation of MSC into hepatocytes was the mode of action but paracrine secretion of factors rescuing the injured liver from end-stage damage.
60. Fox IJ, Roy-Chowdhury J. Hepatocyte transplantation. Am J Transplant 2004; (Suppl 6): 7-13.
61. Lee S-W, Wang X, Chowdhury NR, Chowdhury JR. Hepatocyte transplantation: state of the art and strategies for overcoming existing hurdles. Ann Hepatol 2004; 3:48-53.
62. Muraca M, Gerunda G, Neri D, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet 2002; 317-318.
63. Fox IJ, Chowdhury JR, Kaufman SS, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 1998; 338:1422-1426.
64. Michalopoulos GK. Liver regeneration. J Cell Physiol 2007; 213:286-300.
65. Walldorf J, Hillebrand C, Aurich H, et al. 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.
66. Kraft E, Stickl H. Vergleichende Messungen des Wachstums der Rattenleber mittels des Messquadrates und des Leitzschen Integrationstisches an histologischen Schnitten. Virchows Archiv 1954; 324:650-661.
67. Dong X, Zhang H, Pan R, et al. Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. World J Gastroenterol 2010; 16:3267-3278.
68. 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.
69. Yan Y, Xu W, Qian H, et al. Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver Int 2009; 29:356-365.
70. Stock P, Ebensing S, Hempel M, et al. Hepatocyte-like cells derived from human mesenchymal stem cells support regeneration of the mouse liver after acetaminophen-induced injury. Regen Med 2009; 4:S79.
71. Stock P, Pelz S, Ebensing S, et al. Immunodeficient mice: a suitable model for cell transplantation in nonalcoholic steatohepatisis (NASH). FASEB J 2010; 24:235-236.
72. Wang Y, Yao H-L, Cui C-B, et al. Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates. Hepatology 2010 [Epub ahead of print].
73. Gomez-Aristizabal A, Keating A, Davies JE. Mesenchymal stromal cells as supportive cells for hepatocytes. 2009; 17:1504-1508.
74. Gö therström C Immunomodulation by multipotent mesenchymal stromal cells. Transplantation. 2007; 84:S35-37.
75. 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.
76. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007; 262:509-525. (Pubitemid 47620502)
77. Krampera M, Sartoris S, Liotta F, et al. Immune regulation by mesenchymal stem cells derived from adult spleen and thymus. Stem Cells Dev 2007; 16:797-810.
78. Parekkadan B, van Poll D, Suganuma K, et al. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS ONE 2007; 2:e941.
79. Yagi H, Soto-Gutierrez A, Kitagawa Y, et al. Bone marrow mesenchymal stromal cells attenuate organ injury induced by LPS and burn. Cell Transplant 2010 [Epub ahead of print].
80. Jin SZ, Meng XW, Han MZ, et al. Stromal cell derived factor-1 enhances bone marrow mononuclear cell migration in mice with acute liver failure. World J Gastroenterol 2009; 15:2657-2664.
81. Chen Y, Xiang L-X, Shao J-Z, et al. Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver. J Cell Molec Med 2010; 14:1494-1508.
82. Eckersley-Maslin MA, Warner FJ, Grzelak CA, et al. Bone marrow stem cells and the liver: are they relevant? J Gastroenterol Hepatol 2009; 24:1608-1616.
83. Alison MR, Islam S, Lim S. Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly. J Pathol 2009; 217:282-298.
84. di Bonzo LV, Ferrero I, Cravanzola C, et al. Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 2008; 57:223-231.
85. Russo FP, Alison MR, Bigger BW, et al. The bone marrow functionally contributes to liver fibrosis. Gastroenterology 2006; 130:1807-1821.
86. Ren H, Zhao Q, Cheng T, et al. No contribution of umbilical cord mesenchymal stromal cells to capillarization and venularization of hepatic sinusoids accompanied by hepatic differentiation in carbon tetrachloride-induced mouse liver fibrosis. Cytotherapy 2010; 12:371-383.
87. Carvalho AB, Quintanilha LF, Dias JV, et al. Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury. Stem Cells 2008; 26:1307-1314.
88. Asano Y, Iimuro Y, Son G, et al. Hepatocyte growth factor promotes remodeling of murine liver fibrosis, accelerating recruitment of bone marrowderived cells into the liver. Hepatol Res 2007; 37:1080-1094.
89. Chang Y-J, Liu J-W, Lin P-C, et al. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis. Life Sci 2009; 85:517-525.
90. Pulavendran S, Vignesh J, Rose C. Differential anti-inflammatory and antifibrotic activity of transplanted mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver injury in mice. Int Immunopharmacol 2010; 10:513-519.
91. Deregibus MC, TC, Camussi G. The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information. Histol Histopathol 2010; 25:397-404.
92. Collino F, Deregibus MC, Bruno S, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS ONE 2010; 5:e11803.
93. Alison MR, Islam S, Lim SM. Cell therapy for liver disease. Curr Opin Mol Ther 2009; 11:364-374.
94. Soto-Gutierrez A, Navarro-Alvarez N, Yagi H, Yarmush ML. Stem cells for liver repopulation. Curr Opin Organ Transplant 2009; 14:667-673, 610.
95. Flohr TR, Bonatti HJ, Brayman KL, Pruett TL. The use of stem cells in liver disease. Curr Opin Organ Transplant 2009; 14:64-71.
96. Haridass D, Narain N, Ott M. Hepatocyte transplantation: waiting for stem cells. Curr Opin Organ Transplant 2008; 13:627-632, 610.
97. Qin AC, Liao CX, Wang Y, et al. Intrahepatic transplantation of in vitro induced autologous bone marrow-derived liver stem cells in patients with posthepatitic cirrhosis. Nan Fang Yi Ke Da Xue Xue Bao 2010; 30:529-531 [Article in Chinese].
98. Khan AA, Shaik MV, Parveen N, et al. Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant 2010; 19:409-418.
99. Fisher RA, Strom SC. Human hepatocyte transplantation. Transplantation 2006; 82:441-449.
100. Dahlke MH, Hoogduijn M, Eggenhofer E, et al. Toward MSC in solid organ transplantation: 2008 position paper of the MISOT study group. Transplantation 2009; 88:614-619.
101. Blanc KL, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371:1579-1586.
102. Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. 2007; 449:557-563.
103. Bilir BM, Guinette D, Karrer F, et al. Hepatocyte transplantation in acute liver failure. Liver Transplant 2000; 6:32-40.