Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease

World Journal of Gastroenterology

Volumn 22, Issue 1, 2016, Pages 24-36

  Ezquer, Fernando ^a   Bruna, Flavia ^a   Calligaris, Sebastián ^a   Conget, Paulette ^a   Ezquer, Marcelo ^a  

^a UNIVERSIDAD DEL DESARROLLO   (Chile)

Author keywords

Alcoholic liver disease; Alcoholic steatohepatitis; Cellular therapy; Hepatic function recovery; Mesenchymal stem cells

Indexed keywords

ALCOHOL CONSUMPTION; ALCOHOL LIVER DISEASE; CELL DIFFERENTIATION; CELL REGENERATION; CLINICAL TRIAL (TOPIC); HUMAN; IMMUNOMODULATION; INFLAMMATION; LIVER CELL; LIVER INJURY; LIVER REGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; REVIEW; STELLATE CELL; ANIMAL; DISEASE MODEL; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; LIVER DISEASES, ALCOHOLIC; MESENCHYMAL STROMA CELL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROCEDURES; TRANSLATIONAL RESEARCH;

ANIMALS; CELL DIFFERENTIATION; DISEASE MODELS, ANIMAL; HUMANS; IMMUNOSUPPRESSION; LIVER DISEASES, ALCOHOLIC; LIVER REGENERATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84953439326     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v22.i1.24     Document Type: Review

References (150)

1. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011; 141: 1572-1585 [PMID: 21920463]
2. Moon KM, Kim G, Baik SK, Choi E, Kim MY, Kim HA, Cho MY, Shin SY, Kim JM, Park HJ, Kwon SO, Eom YW. Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis. Clin Mol Hepatol 2013; 19: 389-398 [PMID: 24459644 DOI: 10.3350/cmh.2013.19.4.389]
3. Orman ES, Odena G, Bataller R. Alcoholic liver disease: pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol 2013; 28 Suppl 1: 77-84 [PMID: 23855300 DOI: 10.1111/jgh.12030]
4. Clouston AD, Jonsson JR, Powell EE. Steatosis as a cofactor in other liver diseases: hepatitis C virus, alcohol, hemochromatosis, and others. Clin Liver Dis 2007; 11: 173-189, x [PMID: 17544978 DOI: 10.1016/j.cld.2007.02.007]
5. Gitto S, Micco L, Conti F, Andreone P, Bernardi M. Alcohol and viral hepatitis: a mini-review. Dig Liver Dis 2009; 41: 67-70 [PMID: 18602355]
6. Pateria P, de Boer B, MacQuillan G. Liver abnormalities in drug and substance abusers. Best Pract Res Clin Gastroenterol 2013; 27: 577-596 [PMID: 24090944 DOI: 10.1016/j.dld.2008.05.009]
7. Baraona E, Lieber CS. Alcohol and lipids. Recent Dev Alcohol 1998; 14: 97-134 [PMID: 9751944]
8. You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory elementbinding protein (SREBP). J Biol Chem 2002; 277: 29342-29347 [PMID: 12036955 DOI: 10.1074/jbc.M202411200]
9. Wagner M, Zollner G, Trauner M. Nuclear receptors in liver disease. Hepatology 2011; 53: 1023-1034 [PMID: 21319202 DOI: 10.1002/hep.24148]
10. Kim W, Kim DJ. Severe alcoholic hepatitis-current concepts, diagnosis and treatment options. World J Hepatol 2014; 6: 688-695 [PMID: 25349640 DOI: 10.4254/wjh.v6.i10.688]
11. Spengler EK, Dunkelberg J, Schey R. Alcoholic hepatitis: current management. Dig Dis Sci 2014; 59: 2357-2366 [PMID: 24798996 DOI: 10.1007/s10620-014-3173-8]
12. Rusyn I, Bataller R. Alcohol and toxicity. J Hepatol 2013; 59: 387-388 [PMID: 23391479 DOI: 10.1016/j.jhep.2013.01.035]
13. Farfán Labonne BE, Gutiérrez M, Gómez-Quiroz LE, Konigsberg Fainstein M, Bucio L, Souza V, Flores O, Ortíz V, Hernández E, Kershenobich D, Gutiérrez-Ruíz MC. Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol Toxicol 2009; 25: 599-609 [PMID: 19137438 DOI: 10.1007/s10565-008-9115-5]
14. Setshedi M, Wands JR, Monte SM. Acetaldehyde adducts in alcoholic liver disease. Oxid Med Cell Longev 2010; 3: 178-185 [PMID: 20716942 DOI: 10.4161/oxim.3.3.12288]
15. Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology 2015; 148: 30-36 [PMID: 25447847 DOI : 10.1053/j.gastro.2014.10.042]
16. Kendrick SF, O'Boyle G, Mann J, Zeybel M, Palmer J, Jones DE, Day CP. Acetate, the key modulator of inflammatory responses in acute alcoholic hepatitis. Hepatology 2010; 51: 1988-1997 [PMID: 20232292 DOI: 10.1002/hep.23572]
17. Rao R. Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology 2009; 50: 638-644 [PMID: 19575462 DOI: 10.1002/hep.23009]
18. Zhao XJ, Dong Q, Bindas J, Piganelli JD, Magill A, Reiser J, Kolls JK. TRIF and IRF-3 binding to the TNF promoter results in macrophage TNF dysregulation and steatosis induced by chronic ethanol. J Immunol 2008; 181: 3049-3056 [PMID: 18713975]
19. Hritz I, Mandrekar P, Velayudham A, Catalano D, Dolganiuc A, Kodys K, Kurt-Jones E, Szabo G. The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88. Hepatology 2008; 48: 1224-1231 [PMID: 18792393 DOI: 10.1002/hep.22470]
20. Bataller R, Rombouts K, AltamIrano J, Marra F. Fibrosis in alcoholic and nonalcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 2011; 25: 231-244 [PMID: 21497741]
21. Neuman MG, French SW, French BA, Seitz HK, Cohen LB, Mueller S, Osna NA, Kharbanda KK, Seth D, Bautista A, Thompson KJ, McKillop IH, Kirpich IA, McClain CJ, Bataller R, Nanau RM, Voiculescu M, Opris M, Shen H, Tillman B, Li J, Liu H, Thomes PG, Ganesan M, Malnick S. Alcoholic and non-Alcoholic steatohepatitis. Exp Mol Pathol 2014; 97: 492-510 [PMID: 25217800]
22. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-218 [PMID: 15690074 DOI: 10.1172/JCI24282]
23. Wang JH, Batey RG, George J. Role of ethanol in the regulation of hepatic stellate cell function. World J Gastroenterol 2006; 12: 6926-6932 [PMID: 17109512 DOI: 10.3748/wjg.v12.i43.6926]
24. Arthur MJ, Iredale JP, Mann DA. Tissue inhibitors of metalloproteinases: role in liver fibrosis and alcoholic liver disease. Alcohol Clin Exp Res 1999; 23: 940-943 [PMID: 10371419]
25. Bolondi L, Gramantieri L. From liver cirrhosis to HCC. Intern Emerg Med 2011; 6 Suppl 1: 93-98 [PMID: 22009618 DOI: 10.1007/s11739-011-0682-8]
26. Lee SS, Shin HS, Kim HJ, Lee SJ, Lee HS, Hyun KH, Kim YH, Kwon BW, Han JH, Choi H, Kim BH, Lee JH, Kang HY, Shin HD, Song IH. Analysis of prognostic factors and 5-year survival rate in patients with hepatocellular carcinoma: a single-center experience. Korean J Hepatol 2012; 18: 48-55 [PMID: 22511903 DOI: 10.3350/kjhep.2012.18.1.48]
27. AltamIrano J, Bataller R. Cigarette smoking and chronic liver diseases. Gut 2010; 59: 1159-1162 [PMID: 20650922 DOI: 10.1136/gut.2008.162453]
28. Anstee QM, Daly AK, Day CP. Genetics of alcoholic and nonalcoholic fatty liver disease. Semin Liver Dis 2011; 31: 128-146 [PMID: 21538280 DOI: 10.1055/s-0031-1276643]
29. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, Saveria Crocé L, Sasso F, Pozzato G, Cristianini G, Brandi G. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut 1997; 41: 845-850 [PMID: 9462221]
30. Stroffolini T, Cotticelli G, Medda E, Niosi M, Del Vecchio-Blanco C, Addolorato G, Petrelli E, Salerno MT, Picardi A, Bernardi M, Almasio P, Bellentani S, Surace LA, Loguercio C. Interaction of alcohol intake and cofactors on the risk of cirrhosis. Liver Int 2010; 30: 867-870 [PMID: 20492499 DOI: 10.1111/j.1478-3231.2010.02261.x]
31. Helman RA, Temko MH, Nye SW, Fallon HJ. Alcoholic hepatitis. Natural history and evaluation of prednisolone therapy. Ann Intern Med 1971; 74: 311-321 [PMID: 4928161]
32. Jaurigue MM, Cappell MS. Therapy for alcoholic liver disease. World J Gastroenterol 2014; 20: 2143-2158 [PMID: 24605013 DOI: 10.3748/wjg.v20.i9.2143]
33. Borowsky SA, Strome S, Lott E. Continued heavy drinking and survival in alcoholic cirrhotics. Gastroenterology 1981; 80: 1405-1409 [PMID: 6971772]
34. Pessione F, Ramond MJ, Peters L, Pham BN, Batel P, Rueff B, Valla DC. Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence. Liver Int 2003; 23: 45-53 [PMID: 12640727]
35. Menachery J, Duseja A. Treatment of decompensated alcoholic liver disease. Int J Hepatol 2011; 2011: 219238 [PMID: 21994849 DOI: 10.4061/2011/219238]
36. Morgan MY. The prognosis and outcome of alcoholic liver disease. Alcohol Alcohol Suppl 1994; 2: 335-343 [PMID: 8974353]
37. Singal AK, Walia I, Singal A, Soloway RD. Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis: Current status. World J Hepatol 2011; 3: 205-210 [PMID: 21954408 DOI: 10.4254/wjh.v3.i8.205]
38. Boetticher NC, Peine CJ, Kwo P, Abrams GA, Patel T, Aqel B, Boardman L, Gores GJ, Harmsen WS, McClain CJ, Kamath PS, Shah VH. A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology 2008; 135: 1953-1960 [PMID: 18848937 DOI: 10.1053/j.gastro.2008.08.057]
39. Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol 2004; 40: 40-46 [PMID: 14672612]
40. O'Shea RS, McCullough AJ. Treatment of alcoholic hepatitis. Clin Liver Dis 2005; 9: 103-134 [PMID: 15763232 DOI: 10.1016/j.cld.2004.11.004]
41. Singal AK, Duchini A. Liver transplantation in acute alcoholic hepatitis: Current status and future development. World J Hepatol 2011; 3: 215-218 [PMID: 21954410 DOI: 10.4254/wjh.v3.i8.215]
42. Strom SC, Bruzzone P, Cai H, Ellis E, Lehmann T, Mitamura K, Miki T. Hepatocyte transplantation: clinical experience and potential for future use. Cell Transplant 2006; 15 Suppl 1: S105-S110 [PMID: 16826802]
43. Michalopoulos GK. Liver regeneration. J Cell Physiol 2007; 213: 286-300 [PMID: 17559071 DOI: 10.1002/jcp.21172]
44. Duguay L, Coutu D, Hetu C, Joly JG. Inhibition of liver regeneration by chronic alcohol administration. Gut 1982; 23: 8-13 [PMID: 7056500]
45. Wands JR, Carter EA, Bucher NL, Isselbacher KJ. Effect of acute and chronic ethanol intoxication on hepatic regeneration. Adv Exp Med Biol 1980; 132: 663-670 [PMID: 7191626]
46. Dey A, Cederbaum AI. Alcohol and oxidative liver injury. Hepatology 2006; 43: S63-S74 [PMID: 16447273 DOI: 10.1002/hep.20957]
47. Gao W, Zhou P, Ma X, Tschudy-Seney B, Chen J, Magner NL, Revzin A, Nolta JA, Zern MA, Duan Y. Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro. PLoS One 2014; 9: e112698 [PMID: 25393427 DOI: 10.1371/journal.pone.0112698]
48. Schneider A, Attaran M, Meier PN, Strassburg C, Manns MP, Ott M, Barthold M, Arseniev L, Becker T, Panning B. Hepatocyte transplantation in an acute liver failure due to mushroom poisoning. Transplantation 2006; 82: 1115-1116 [PMID: 17060866 DOI: 10.1097/01.tp.0000232451.93703.ab]
49. Serralta A, Donato MT, Orbis F, Castell JV, Mir J, Gómez-Lechón MJ. Functionality of cultured human hepatocytes from elective samples, cadaveric grafts and hepatectomies. Toxicol In Vitro 2003; 17: 769-774 [PMID: 14599475]
50. Serralta A, Donato MT, Martinez A, Pareja E, Orbis F, Castell JV, Mir J, Gómez-Lechón MJ. Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts. Cell Transplant 2005; 14: 837-843 [PMID: 16454358]
51. Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. Hepatocytes from non-hepatic adult stem cells. Nature 2000; 406: 257 [PMID: 10917519 DOI: 10.1038/35018642]
52. Hannan NR, Segeritz CP, Touboul T, Vallier L. Production of hepatocyte-like cells from human pluripotent stem cells. Nat Protoc 2013; 8: 430-437 [PMID: 23424751]
53. Almeida-Porada G, Zanjani ED, Porada CD. Bone marrow stem cells and liver regeneration. Exp Hematol 2010; 38: 574-580 [PMID: 20417684 DOI: 10.1016/j.exphem.2010.04.007]
54. Berardis S, Dwisthi Sattwika P, Najimi M, Sokal EM. Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects. World J Gastroenterol 2015; 21: 742-758 [PMID: 25624709 DOI: 10.3748/wjg.v21.i3.742]
55. Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair-current views. Stem Cells 2007; 25: 2896-2902 [PMID: 17901396 DOI: 10.1634/stemcells.2007-0637]
56. Fiore EJ, Mazzolini G, Aquino JB. Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives. Stem Cell Rev 2015; 11: 586-597 [PMID: 25820543 DOI: 10.1007/s12015-015-9585-9]
57. Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res 2009; 2: 16-25 [PMID: 19383405 DOI: 10.1016/j.scr.2008.07.005]
58. Levine P, McDaniel K, Francis H, Kennedy L, Alpini G, Meng F. Molecular mechanisms of stem cell therapy in alcoholic liver disease. Dig Liver Dis 2014; 46: 391-397 [PMID: 24440312 DOI: 10.1016/j.dld.2013.11.015]
59. He N, Zhang L, Cui J, Li Z. Bone marrow vascular niche: home for hematopoietic stem cells. Bone Marrow Res 2014; 2014: 128436 [PMID: 24822129 DOI: 10.1155/2014/128436]
60. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17: 331-340 [PMID: 4150881]
61. De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P, Chen I, Fraser J, Hedrick MH. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 2003; 174: 101-109 [PMID: 12835573]
62. in 't Anker PS, Noort WA, Scherjon SA, Kleijburg-van der Keur C, Kruisselbrink AB, van Bezooijen RL, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE. Mesenchymal stem cells in human secondtrimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 2003; 88: 845-852 [PMID: 12935972]
63. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 2004; 103: 1669-1675 [PMID: 14576065 DOI: 10.1182/blood-2003-05-1670]
64. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317 [PMID: 16923606 DOI: 10.1080/146 53240600855905]
65. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood) 2001; 226: 507-520 [PMID: 11395921]
66. Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, Gautam SC, Chopp M. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003; 73: 778-786 [PMID: 12949903 DOI: 10.1002/jnr.10691]
67. Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 2006; 108: 3938-3944 [PMID: 16896152 DOI: 10.1182/blood-2006-05-025098]
68. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98: 1076-1084 [PMID: 16619257 DOI: 10.1002/jcb.20886]
69. Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci 2011; 18: 49 [PMID: 21762539 DOI: 10.1186/1423-0127-18-49]
70. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8: 726-736 [PMID: 19172693 DOI: 10.1038/nri2395]
71. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147 [PMID: 10102814]
72. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-49 [PMID: 12077603 DOI: 10.1038/nature00870]
73. Hengstler JG, Brulport M, Schormann W, Bauer A, Hermes M, Nussler AK, Fandrich F, Ruhnke M, Ungefroren H, Griffin L, Bockamp E, Oesch F, von Mach MA. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte. Expert Opin Drug Metab Toxicol 2005; 1: 61-74 [PMID: 16922653 DOI: 10.1517/17425255.1.1.61]
74. Taléns-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gómez-Lechón MJ. Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage. Toxicol In Vitro 2007; 21: 324-329 [PMID: 17045453 DOI: 10.1016/j.tiv.2006.08.009]
75. 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 2002; 109: 1291-1302 [PMID: 12021244 DOI: 10.1172/JCI15182]
76. Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, Takimoto R, Iyama S, Matsunaga T, Ohtani S, Matsuura A, Hamada H, Niitsu Y. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 2005; 106: 756-763 [PMID: 15817682 DOI: 10.1182/blood-2005-02-0572]
77. Shu SN, Wei L, Wang JH, Zhan YT, Chen HS, Wang Y. Hepatic differentiation capability of rat bone marrow-derived mesenchymal stem cells and hematopoietic stem cells. World J Gastroenterol 2004; 10: 2818-2822 [PMID: 15334677 DOI: 10.3748/wjg.v10.i19.2818]
78. Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000; 31: 235-240 [PMID: 10613752 DOI: 10.1002/hep.510310135]
79. Chamberlain J, Yamagami T, Colletti E, Theise ND, Desai J, Frias A, Pixley J, Zanjani ED, Porada CD, Almeida-Porada G. Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep. Hepatology 2007; 46: 1935-1945 [PMID: 17705296 DOI: 10.1002/hep.21899]
80. Liang XJ, Chen XJ, Yang DH, Huang SM, Sun GD, Chen YP. Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells by hTERT gene transfection in vitro. Cell Biol Int 2012; 36: 215-221 [PMID: 21988655 DOI: 10.1042/CBI20110350]
81. Bornstein R, Macias MI, de la Torre P, Grande J, Flores AI. Human decidua-derived mesenchymal stromal cells differentiate into hepatic-like cells and form functional three-dimensional structures. Cytotherapy 2012; 14: 1182-1192 [PMID: 22900961 DOI: 10.3109/14653249.2012.706706]
82. Ayatollahi M, Soleimani M, Tabei SZ, Kabir Salmani M. Hepatogenic differentiation of mesenchymal stem cells induced by insulin like growth factor-I. World J Stem Cells 2011; 3: 113-121 [PMID: 22224170 DOI: 10.4252/wjsc.v3.i12.113]
83. Piryaei A, Valojerdi MR, Shahsavani M, Baharvand H. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells on nanofibers and their transplantation into a carbon tetrachloride-induced liver fibrosis model. Stem Cell Rev 2011; 7: 103-118 [PMID: 20182823 DOI: 10.1007/s12015-010-9126-5]
84. Prasajak P, Leeanansaksiri W. Developing a New Two-Step Protocol to Generate Functional Hepatocytes from Wharton's Jelly-Derived Mesenchymal Stem Cells under Hypoxic Condition. Stem Cells Int 2013; 2013: 762196 [PMID: 23818908 DOI: 10.1155/2013/762196]
85. Campard D, Lysy PA, Najimi M, Sokal EM. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology 2008; 134: 833-848 [PMID: 18243183 DOI: 10.1053/j.gastro.2007.12.024]
86. Berisio R, Schluenzen F, Harms J, Bashan A, Auerbach T, Baram D, Yonath A. Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat Struct Biol 2003; 10: 366-370 [PMID: 12665853 DOI: 10.1038/nature01539]
87. 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 [PMID: 12665832 DOI: 10.1038/nature01531]
88. Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med 2010; 14: 2190-2199 [PMID: 20716123 DOI: 10.1111/j.1582-4934.2010.01151.x]
89. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell 2011; 9: 11-15 [PMID: 21726829 DOI: 10.1016/j.stem.2011.06.008]
90. Lee T. Stem cell therapy independent of stemness. World J Stem Cells 2012; 4: 120-124 [PMID: 23516128 DOI: 10.4252/wjsc. v4.i12.120]
91. Szabo G, Petrasek J, Bala S. Innate immunity and alcoholic liver disease. Dig Dis 2012; 30 Suppl 1: 55-60 [PMID: 23075869 DOI: 10.1159/000341126]
92. Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, Alao H, Kodys K, Szabo G. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56: 1946-1957 [PMID: 22684891 DOI: 10.1002/hep.25873]
93. Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 2012; 20: 14-20 [PMID: 22008910 DOI: 10.1038/mt.2011.211]
94. Liu YL, Jiang XX, Su YF, Huo SW, Zhu H, Wu Y, Mao N, Zhang Y. Endothelial cells from human umbilical vein inhibit generation of monocyte-derived dendritic cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2011; 19: 480-484 [PMID: 21518513]
95. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 2004; 13: 263-271 [PMID: 15186722 DOI: 10.1089/154732804 323099190]
96. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killercell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008; 111: 1327-1333 [PMID: 17951526 DOI: 10.1182/blood-2007-02-074997]
97. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815-1822 [PMID: 15494428 DOI: 10.1182/blood-2004-04-1559]
98. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103: 4619-4621 [PMID: 15001472 DOI: 10.1182/blood-2003-11-3909]
99. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107: 367-372 [PMID: 16141348 DOI: 10.1182/blood-2005-07-2657]
100. Ezquer F, Ezquer M, Contador D, Ricca M, Simon V, Conget P. The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment. Stem Cells 2012; 30: 1664-1674 [PMID: 22644660 DOI: 10.1002/stem.1132]
101. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31: 890-896 [PMID: 14550804]
102. Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 2001; 169: 12-20 [PMID: 11340257]
103. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009; 5: 54-63 [PMID: 19570514 DOI: 10.1016/j.stem.2009.05.003]
104. Schrepfer S, Deuse T, Reichenspurner H, Fischbein MP, Robbins RC, Pelletier MP. Stem cell transplantation: the lung barrier. Transplant Proc 2007; 39: 573-576 [PMID: 17362785 DOI: 10.1016/j.transproceed.2006.12.019]
105. van Poll D, Parekkadan B, Cho CH, Berthiaume F, Nahmias Y, Tilles AW, Yarmush ML. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 2008; 47: 1634-1643 [PMID: 18395843 DOI: 10.1002/hep.22236]
106. Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 2013; 44: 11-19 [PMID: 23203002 DOI: 10.1007/s12020-012-9839-0]
107. Camussi G, Deregibus MC, Cantaluppi V. Role of stem-cellderived microvesicles in the paracrine action of stem cells. Biochem Soc Trans 2013; 41: 283-287 [PMID: 23356298 DOI: 10.1042/BST20120192]
108. Herrera MB, Fonsato V, Gatti S, Deregibus MC, Sordi A, Cantarella D, Calogero R, Bussolati B, Tetta C, Camussi G. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med 2010; 14: 1605-1618 [PMID: 19650833 DOI: 10.1111/j.1582-4934.2009.00860.x]
109. Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W, Xu W. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22: 845-854 [PMID: 23002959 DOI: 10.1089/scd.2012.0395]
110. Ezquer M, Ezquer F, Ricca M, Allers C, Conget P. Intravenous administration of multipotent stromal cells prevents the onset of nonalcoholic steatohepatitis in obese mice with metabolic syndrome. J Hepatol 2011; 55: 1112-1120 [PMID: 21356258 DOI: 10.1016/j.jhep.2011.02.020]
111. Seki A, Sakai Y, Komura T, Nasti A, Yoshida K, Higashimoto M, Honda M, Usui S, Takamura M, Takamura T, Ochiya T, Furuichi K, Wada T, Kaneko S. Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model. Hepatology 2013; 58: 1133-1142 [PMID: 23686813 DOI: 10.1002/hep.26470]
112. Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y, Yu S, Geng H, Jin L, Lau GK, Wang FS. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 2012; 27 Suppl 2: 112-120 [PMID: 22320928 DOI: 10.1111/j.1440-1746.2011.07024.x]
113. Forbes SJ, Russo FP, Rey V, Burra P, Rugge M, Wright NA, Alison MR. A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 2004; 126: 955-963 [PMID: 15057733]
114. di Bonzo LV, Ferrero I, Cravanzola C, Mareschi K, Rustichell D, Novo E, Sanavio F, Cannito S, Zamara E, Bertero M, Davit A, Francica S, Novelli F, Colombatto S, Fagioli F, Parola M. 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 [PMID: 17639088 DOI: 10.1136/gut.2006.111617]
115. Baertschiger RM, Serre-Beinier V, Morel P, Bosco D, Peyrou M, Clément S, Sgroi A, Kaelin A, Buhler LH, Gonelle-Gispert C. Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver. PLoS One 2009; 4: e6657 [PMID: 19684854 DOI: 10.1371/journal.pone.0006657]
116. Carvalho AB, Quintanilha LF, Dias JV, Paredes BD, Mannheimer EG, Carvalho FG, Asensi KD, Gutfilen B, Fonseca LM, Resende CM, Rezende GF, Takiya CM, de Carvalho AC, Goldenberg RC. 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 [PMID: 18308943 DOI: 10.1634/stemcells.2007-0941]
117. Kim S, Kim HS, Lee E, Kim HO. In vivo hepatic differentiation potential of human cord blood-derived mesenchymal stem cells. Int J Mol Med 2011; 27: 701-706 [PMID: 21347513 DOI: 10.3892/ijmm.2011.627]
118. Arteel GE. Animal models of alcoholic liver disease. Dig Dis 2010; 28: 729-736 [PMID: 21525757 DOI: 10.1159/000324280]
119. Mathews S, Xu M, Wang H, Bertola A, Gao B. Animals models of gastrointestinal and liver diseases. Animal models of alcoholinduced liver disease: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol 2014; 306: G819-G823 [PMID: 24699333 DOI: 10.1152/ajpgi.00041.2014]
120. Starkel P, Leclercq IA. Animal models for the study of hepatic fibrosis. Best Pract Res Clin Gastroenterol 2011; 25: 319-333 [PMID: 21497748 DOI: 10.1016/j.bpg.2011.02.004]
121. Tanimoto H, Terai S, Taro T, Murata Y, Fujisawa K, Yamamoto N, Sakaida I. Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow. Cell Tissue Res 2013; 354: 717-728 [PMID: 24104560 DOI: 10.1007/s00441-013-1727-2]
122. Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, Tilles AW, Yarmush ML. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One 2007; 2: e941 [PMID: 17895982 DOI: 10.1371/journal.pone.0000941]
123. Han Z, Jing Y, Zhang S, Liu Y, Shi Y, Wei L. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell Biosci 2012; 2: 8 [PMID: 22390479 DOI: 10.1186/2045-3701-2-8]
124. Lin N, Hu K, Chen S, Xie S, Tang Z, Lin J, Xu R. Nerve growth factor-mediated paracrine regulation of hepatic stellate cells by multipotent mesenchymal stromal cells. Life Sci 2009; 85: 291-295 [PMID: 19559033 DOI: 10.1016/j.lfs.2009.06.007]
125. Parekkadan B, van Poll D, Megeed Z, Kobayashi N, Tilles AW, Berthiaume F, Yarmush ML. Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun 2007; 363: 247-252 [PMID: 17869217 DOI: 10.1016/j.bbrc.2007.05.150]
126. Zhang D, Jiang M, Miao D. Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse. PLoS One 2011; 6: e16789 [PMID: 21326862 DOI: 10.1371/journal.pone.0016789]
127. Fiore EJ, Bayo JM, Garcia MG, Malvicini M, Lloyd R, Piccioni F, Rizzo M, Peixoto E, Sola MB, Atorrasagasti C, Alaniz L, Camilletti MA, Enguita M, Prieto J, Aquino JB, Mazzolini G. Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice. Stem Cells Dev 2015; 24: 791-801 [PMID: 25315017 DOI: 10.1089/scd.2014.0174]
128. Higashiyama R, Inagaki Y, Hong YY, Kushida M, Nakao S, Niioka M, Watanabe T, Okano H, Matsuzaki Y, Shiota G, Okazaki I. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology 2007; 45: 213-222 [PMID: 17187438 DOI: 10.1002/hep.21477]
129. Chang YJ, Liu JW, Lin PC, Sun LY, Peng CW, Luo GH, Chen TM, Lee RP, Lin SZ, Harn HJ, Chiou TW. Mesenchymal stem cells facilitate recovery from chemically induced liver damage and decrease liver fibrosis. Life Sci 2009; 85: 517-525 [PMID: 19686763 DOI: 10.1016/j.lfs.2009.08.003]
130. Chagoya de Sánchez V, Martínez-Pérez L, Hernández-Muñoz R, Velasco-Loyden G. Recovery of the Cell Cycle Inhibition in CCl(4)-Induced Cirrhosis by the Adenosine Derivative IFC-305. Int J Hepatol 2012; 2012: 212530 [PMID: 23056951 DOI: 10.1155/2012/212530]
131. Wang Y, Lian F, Li J, Fan W, Xu H, Yang X, Liang L, Chen W, Yang J. Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats. J Transl Med 2012; 10: 133 [PMID: 22735033 DOI: 10.1186/1479-5876-10-133]
132. Le Blanc K, Götherström C, Ringdén O, Hassan M, McMahon R, Horwitz E, Anneren G, Axelsson O, Nunn J, Ewald U, Nordén-Lindeberg S, Jansson M, Dalton A, Aström E, Westgren M. Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation 2005; 79: 1607-1614 [PMID: 15940052]
133. Fouillard L, Francois S, Bouchet S, Bensidhoum M, Elm'selmi A, Chapel A. Innovative cell therapy in the treatment of serious adverse events related to both chemo-radiotherapy protocol and acute myeloid leukemia syndrome: the infusion of mesenchymal stem cells post-treatment reduces hematopoietic toxicity and promotes hematopoietic reconstitution. Curr Pharm Biotechnol 2013; 14: 842-848 [PMID: 24372262]
134. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versushost disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439-1441 [PMID: 15121408]
135. Lee ST, Jang JH, Cheong JW, Kim JS, Maemg HY, Hahn JS, Ko YW, Min YH. Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol 2002; 118: 1128-1131 [PMID: 12199796]
136. Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 2003; 100: 8407-8411 [PMID: 12815096 DOI: 10.1073/pnas.1432929100]
137. Gnecchi M, Danieli P, Cervio E. Mesenchymal stem cell therapy for heart disease. Vascul Pharmacol 2012; 57: 48-55 [PMID: 22521741 DOI: 10.1016/j.vph.2012.04.002]
138. Amin MA, Sabry D, Rashed LA, Aref WM, el-Ghobary MA, Farhan MS, Fouad HA, Youssef YA. Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study. Clin Transplant 2013; 27: 607-612 [PMID: 23923970 DOI: 10.1111/ctr.12179]
139. El-Ansary M, Abdel-Aziz I, Mogawer S, Abdel-Hamid S, Hammam O, Teaema S, Wahdan M. Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev 2012; 8: 972-981 [PMID: 21989829 DOI: 10.1007/s12015-011-9322-y]
140. Jang YO, Kim YJ, Baik SK, Kim MY, Eom YW, Cho MY, Park HJ, Park SY, Kim BR, Kim JW, Soo Kim H, Kwon SO, Choi EH, Kim YM. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int 2014; 34: 33-41 [PMID: 23782511 DOI: 10.1111/liv.12218]
141. Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol 2009; 21: 1199-1205 [PMID: 19455046 DOI: 10.1097/MEG.0b013e32832a1f6c]
142. Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, Bagheri M, Bashtar M, Ghanaati H, Baharvand H, Ghavamzadeh A, Malekzadeh R. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 2007; 10: 459-466 [PMID: 17903050]
143. Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology 2011; 54: 820-828 [PMID: 21608000 DOI: 10.1002/hep.24434]
144. Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang FS. Human mesenchymal stem cell transfusion is safe and improves liver function in acuteon-chronic liver failure patients. Stem Cells Transl Med 2012; 1: 725-731 [PMID: 23197664 DOI: 10.5966/sctm.2012-0034]
145. Wang L, Li J, Liu H, Li Y, Fu J, Sun Y, Xu R, Lin H, Wang S, Lv S, Chen L, Zou Z, Li B, Shi M, Zhang Z, Wang FS. Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis. J Gastroenterol Hepatol 2013; 28 Suppl 1: 85-92 [PMID: 23855301 DOI: 10.1111/jgh.12029]
146. Cui Q, Wang GJ, Balian G. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J Bone Joint Surg Am 1997; 79: 1054-1063 [PMID: 9234882]
147. Cuiffo BG, Karnoub AE. Mesenchymal stem cells in tumor development: emerging roles and concepts. Cell Adh Migr 2012; 6: 220-230 [PMID: 22863739 DOI: 10.4161/cam.20875]
148. Kunter U, Rong S, Boor P, Eitner F, Müller-Newen G, Djuric Z, van Roeyen CR, Konieczny A, Ostendorf T, Villa L, Milovanceva-Popovska M, Kerjaschki D, Floege J. Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol 2007; 18: 1754-1764 [PMID: 17460140 DOI: 10.1681/ASN.2007010044]
149. Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, Welz A, Bloch W, Jacobsen SE, Fleischmann BK. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 2007; 110: 1362-1369 [PMID: 17483296 DOI: 10.1182/blood-2006-12-063412]
150. Epperly MW, Guo H, Gretton JE, Greenberger JS. Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am J Respir Cell Mol Biol 2003; 29: 213-224 [PMID: 12649121 DOI: 10.1165/rcmb.2002-0069OC]