Stem cell-based regenerative opportunities for the liver: State of the art and beyond

World Journal of Gastroenterology

Volumn 21, Issue 43, 2015, Pages 12334-12350

  Tsolaki, Eleftheria ^a   Yannaki, Evangelia ^a  

^a G PAPANICOLAOU HOSPITAL   (Greece)

Author keywords

Acute liver injury; Liver cirrhosis; Liver regeneration; Stem cell based therapy; Stem cells

Indexed keywords

GRANULOCYTE COLONY STIMULATING FACTOR;

ACUTE LIVER FAILURE; CELL DIFFERENTIATION; EMBRYONIC STEM CELL; ENDOTHELIAL PROGENITOR CELL; FETUS LIVER; FOLLOW UP; HEMATOPOIETIC STEM CELL; HUMAN; LIVER CELL; LIVER CIRRHOSIS; LIVER DISEASE; LIVER REGENERATION; LIVER TRANSPLANTATION; MESENCHYMAL STROMA CELL; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PLURIPOTENT STEM CELL; REGENERATIVE MEDICINE; REVIEW; STELLATE CELL; STEM CELL TRANSPLANTATION; TISSUE ENGINEERING; ANIMAL; CELL LINEAGE; CELL PROLIFERATION; LIVER; LIVER DISEASES; MASS COMMUNICATION; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PHYSIOLOGY; STEM CELL; TRENDS;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; DIFFUSION OF INNOVATION; HUMANS; LIVER; LIVER DISEASES; LIVER REGENERATION; PHENOTYPE; REGENERATIVE MEDICINE; STEM CELL TRANSPLANTATION; STEM CELLS;

EID: 84949058150     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v21.i43.12334     Document Type: Review

References (202)

1. Kim WR, Therneau TM, Benson JT, Kremers WK, Rosen CB, Gores GJ, Dickson ER. Deaths on the liver transplant waiting list: An analysis of competing risks. Hepatology 2006; 43: 345-351 [PMID: 16440361].
2. Zarrinpar A, Busuttil RW. Liver transplantation: past, present and future. Nat Rev Gastroenterol Hepatol 2013; 10: 434-440 [PMID: 23752825 DOI:10.1038/nrgastro.2013.88].
3. Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology 2006; 43: S45-S53 [PMID: 16447274].
4. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997; 276: 60-66 [PMID: 9082986].
5. Gramignoli R, Vosough M, Kannisto K, Srinivasan RC, Strom SC. Clinical hepatocyte transplantation: practical limits and possible solutions. Eur Surg Res 2015; 54: 162-177 [PMID: 25633583 DOI:10.1159/000369552].
6. Gupta S, Gorla GR, Irani AN. Hepatocyte transplantation: emerging insights into mechanisms of liver repopulation and their relevance to potential therapies. J Hepatol 1999; 30: 162-170 [PMID: 9927165].
7. Stéphenne X, Najimi M, Sokal EM. Hepatocyte cryopreservation: is it time to change the strategy? World J Gastroenterol 2010; 16: 1-14 [PMID: 20039443].
8. Terry C, Dhawan A, Mitry RR, Hughes RD. Cryopreservation of isolated human hepatocytes for transplantation: State of the art. Cryobiology 2006; 53: 149-159 [PMID: 16793034].
9. Bird TG, Lorenzini S, Forbes SJ. Activation of stem cells in hepatic diseases. Cell Tissue Res 2008; 331: 283-300 [PMID: 18046579].
10. Dan YY, Yeoh GC. Liver stem cells: A scientific and clinical perspective. J Gastroenterol Hepatol 2008; 23: 687-698 [PMID: 18410603 DOI:10.1111/j.1440-1746.2008.05383.x].
11. Papp V, Rókusz A, Dezso K, Bugyik E, Szabó V, Pávai Z, Paku S, Nagy P. Expansion of hepatic stem cell compartment boosts liver regeneration. Stem Cells Dev 2014; 23: 56-65 [PMID: 23952741 DOI:10.1089/scd.2013.0202].
12. Kung JW, Forbes SJ. Stem cells and liver repair. Curr Opin Biotechnol 2009; 20: 568-574 [PMID: 19837579 DOI:10.1016/j.copbio.2009.09.004].
13. Duncan AW, Dorrell C, Grompe M. Stem cells and liver regeneration. Gastroenterology 2009; 137: 466-481 [PMID: 19470389 DOI:10.1053/j.gastro.2009.05.044].
14. Kordes C, Häussinger D. Hepatic stem cell niches. J Clin Invest 2013; 123: 1874-1880 [PMID: 23635785 DOI:10.1172/JCI66027].
15. Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ, Iredale JP, Lowell S, Roskams T, Forbes SJ. Macrophagederived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 2012; 18: 572-579 [PMID: 22388089 DOI:10.1038/nm.2667].
16. Spee B, Carpino G, Schotanus BA, Katoonizadeh A, Vander Borght S, Gaudio E, Roskams T. Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling. Gut 2010; 59: 247-257 [PMID: 19880964 DOI:10.1136/gut.2009.188367].
17. Wanless IR, Nakashima E, Sherman M. Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med 2000; 124: 1599-1607 [PMID: 11079009].
18. Falkowski O, An HJ, Ianus IA, Chiriboga L, Yee H, West AB, Theise ND. Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells. J Hepatol 2003; 39: 357-364 [PMID: 12927921 DOI:10.1016/S0168-8278(03)00309-X].
19. Stueck AE, Wanless IR. Hepatocyte buds derived from progenitor cells repopulate regions of parenchymal extinction in human cirrhosis. Hepatology 2015; 61: 1696-1707 [PMID: 25644399 DOI:10.1002/hep.27706].
20. Kordes C, Sawitza I, Götze S, Häussinger D. Hepatic stellate cells support hematopoiesis and are liver-resident mesenchymal stem cells. Cell Physiol Biochem 2013; 31: 290-304 [PMID: 23485574 DOI:10.1159/000343368].
21. Kordes C, Sawitza I, Götze S, Herebian D, Häussinger D. Hepatic stellate cells contribute to progenitor cells and liver regeneration. J Clin Invest 2014; 124: 5503-5515 [PMID: 25401473 DOI:10.1172/JCI74119].
22. Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth ME, Reid LM. Human hepatic stem cells from fetal and postnatal donors. J Exp Med 2007; 204: 1973-1987 [PMID: 17664288].
23. Shiojiri N, Koike T. Differentiation of biliary epithelial cells from the mouse hepatic endodermal cells cultured in vitro. Tohoku J Exp Med 1997; 181: 1-8 [PMID: 9149334].
24. Shiojiri N, Mizuno T. Differentiation of functional hepatocytes and biliary epithelial cells from immature hepatocytes of the fetal mouse in vitro. Anat Embryol (Berl) 1993; 187: 221-229 [PMID: 8470822].
25. Haruna Y, Saito K, Spaulding S, Nalesnik MA, Gerber MA. Identification of bipotential progenitor cells in human liver development. Hepatology 1996; 23: 476-481 [PMID: 8617427].
26. Oertel M, Menthena A, Chen YQ, Teisner B, Jensen CH, Shafritz DA. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver. Gastroenterology 2008; 134: 823-832 [PMID: 18262526 DOI:10.1053/j.gastro.2008.01.007].
27. Cantz T, Zuckerman DM, Burda MR, Dandri M, Göricke B, Thalhammer S, Heckl WM, Manns MP, Petersen J, Ott M. Quantitative gene expression analysis reveals transition of fetal liver progenitor cells to mature hepatocytes after transplantation in uPA/RAG-2 mice. Am J Pathol 2003; 162: 37-45 [PMID: 12507888].
28. Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am J Pathol 2001; 159: 1323-1334 [PMID: 11583960].
29. Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Habeeb MA, Srinivas G, Raj TA, Tiwari SK, Kumaresan K, Venkateswarlu J, Pande G, Habibullah CM. Human fetal liverderived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant 2010; 19: 409-418 [PMID: 20447340 DOI:10.3727/096368910X498241].
30. Cardinale V, Carpino G, Gentile R, Napoletano C, Rahimi H, Franchitto A, Semeraro R, Nuti M, Onori P, Berloco PB, Rossi M, Bosco D, Brunelli R, Fraveto A, Napoli C, Torrice A, Gatto M, Venere R, Bastianelli C, Aliberti C, Salvatori FM, Bresadola L, Bezzi M, Attili AF, Reid L, Gaudio E, Alvaro D. Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis. BMC Gastroenterol 2014; 14: 204 [PMID: 25471120 DOI:10.1186/s12876-014-0204-z].
31. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-1147 [PMID: 9804556].
32. Woo DH, Kim SK, Lim HJ, Heo J, Park HS, Kang GY, Kim SE, You HJ, Hoeppner DJ, Kim Y, Kwon H, Choi TH, Lee JH, Hong SH, Song KW, Ahn EK, Chenoweth JG, Tesar PJ, McKay RD, Kim JH. Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice. Gastroenterology 2012; 142: 602-611 [PMID: 22138358 DOI:10.1053/j.gastro.2011.11.030].
33. Hay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, Black JR, Wojtacha D, Samuel K, Hannoun Z, Pryde A, Filippi C, Currie IS, Forbes SJ, Ross JA, Newsome PN, Iredale JP. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci USA 2008; 105: 12301-12306 [PMID: 18719101 DOI:10.1073/pnas.0806522105].
34. Brolén G, Sivertsson L, Björquist P, Eriksson G, Ek M, Semb H, Johansson I, Andersson TB, Ingelman-Sundberg M, Heins N. Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage. J Biotechnol 2010; 145: 284-294 [PMID: 19932139 DOI:10.1016/j.jbiotec.2009].
35. Moriya K, Yoshikawa M, Saito K, Ouji Y, Nishiofuku M, Hayashi N, Ishizaka S, Fukui H. Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl4-treated mice. World J Gastroenterol 2007; 13: 866-873 [PMID: 17352015].
36. Yamamoto H, Quinn G, Asari A, Yamanokuchi H, Teratani T, Terada M, Ochiya T. Differentiation of embryonic stem cells into hepatocytes: biological functions and therapeutic application. Hepatology 2003; 37: 983-993 [PMID: 12717379].
37. Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells. J Clin Invest 2010; 120: 51-59 [PMID: 20051636 DOI:10.1172/JCI40553].
38. Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science 2008; 322: 1490-1494 [PMID: 19056973 DOI:10.1126/science].
39. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-872 [PMID: 18035408].
40. Okita K, Ichisaka T, Yamanaka S. Generation of germlinecompetent induced pluripotent stem cells. Nature 2007; 448: 313-317 [PMID: 17554338].
41. Baum C, Kustikova O, Modlich U, Li Z, Fehse B. Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther 2006; 17: 253-263 [PMID: 16544975].
42. Papapetrou EP, Lee G, Malani N, Setty M, Riviere I, Tirunagari LM, Kadota K, Roth SL, Giardina P, Viale A, Leslie C, Bushman FD, Studer L, Sadelain M. Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells. Nat Biotechnol 2011; 29: 73-78 [PMID: 21151124 DOI:10.1038/nbt.1717].
43. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science 2008; 322: 945-949 [PMID: 18818365 DOI:10.1126/science.1162494].
44. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 2009; 4: 472-476 [PMID: 19481515 DOI:10.1016/j.stem.2009.05.005].
45. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 2010; 7: 618-630 [PMID: 20888316 DOI:10.1016/j.stem.2010.08.012].
46. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 2013; 341: 651-654 [PMID: 23868920 DOI:10.1126/science.1239278].
47. Sterneckert JL, Reinhardt P, Schöler HR. Investigating human disease using stem cell models. Nat Rev Genet 2014; 15: 625-639 [PMID: 25069490 DOI:10.1038/nrg3764].
48. Ko HC, Gelb BD. Concise review: drug discovery in the age of the induced pluripotent stem cell. Stem Cells Transl Med 2014; 3: 500-509 [PMID: 24493856 DOI:10.5966/sctm.2013-0162].
49. Song Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, Song X, Guo Y, Zhao Y, Qin H, Yin X, Wu C, Che J, Lu S, Ding M, Deng H. Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 2009; 19: 1233-1242 [PMID: 19736565 DOI:10.1038/cr.2009.107].
50. Zhang Q, Yang Y, Zhang J, Wang GY, Liu W, Qiu DB, Hei ZQ, Ying QL, Chen GH. Efficient derivation of functional hepatocytes from mouse induced pluripotent stem cells by a combination of cytokines and sodium butyrate. Chin Med J (Engl) 2011; 124: 3786-3793 [PMID: 22340242].
51. Takayama K, Inamura M, Kawabata K, Katayama K, Higuchi M, Tashiro K, Nonaka A, Sakurai F, Hayakawa T, Furue MK, Mizuguchi H. Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction. Mol Ther 2012; 20: 127-137 [PMID: 22068426 DOI:10.1038/mt.2011.234].
52. Chen YF, Tseng CY, Wang HW, Kuo HC, Yang VW, Lee OK. Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology 2012; 55: 1193-1203 [PMID: 22095466 DOI:10.1002/hep.24790].
53. Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest 2010; 120: 3120-3126 [PMID: 20739754 DOI:10.1172/JCI43267].
54. Asgari S, Moslem M, Bagheri-Lankarani K, Pournasr B, Miryounesi M, Baharvand H. Differentiation and transplantation of human induced pluripotent stem cell-derived hepatocyte-like cells. Stem Cell Rev 2013; 9: 493-504 [PMID: 22076752 DOI:10.1007/s12015-011-9330-y].
55. Chiang CH, Wu WW, Li HY, Chien Y, Sun CC, Peng CH, Lin AT, Huang CS, Lai YH, Chiou SH, Hung SI, Chang YL, Lan YT, Liu DM, Chien CS, Huo TI, Lee SD, Wang CY. Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure. Cell Transplant 2015; 24: 541-559 [PMID: 25668102 DOI:10.3727/096368915X686986].
56. Uygun BE, Yarmush ML, Uygun K. Application of whole-organ tissue engineering in hepatology. Nat Rev Gastroenterol Hepatol 2012; 9: 738-744 [PMID: 22890112 DOI:10.1038/nrgastro.2012.140].
57. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013; 499: 481-484 [PMID: 23823721 DOI:10.1038/nature12271].
58. Garate Z, Davis BR, Quintana-Bustamante O, Segovia JC. New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells. Hum Gene Ther 2013; 24: 571-583 [PMID: 23675640 DOI:10.1089/hum.2012.251].
59. van de Ven C, Collins D, Bradley MB, Morris E, Cairo MS. The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. Exp Hematol 2007; 35: 1753-1765 [PMID: 17949892].
60. Newsome PN, Johannessen I, Boyle S, Dalakas E, McAulay KA, Samuel K, Rae F, Forrester L, Turner ML, Hayes PC, Harrison DJ, Bickmore WA, Plevris JN. Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion. Gastroenterology 2003; 124: 1891-1900 [PMID: 12806622].
61. Di Campli C, Piscaglia AC, Pierelli L, Rutella S, Bonanno G, Alison MR, Mariotti A, Vecchio FM, Nestola M, Monego G, Michetti F, Mancuso S, Pola P, Leone G, Gasbarrini G, Gasbarrini A. A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury. Dig Liver Dis 2004; 36: 603-613 [PMID: 15460845].
62. 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].
63. Teramoto K, Asahina K, Kumashiro Y, Kakinuma S, Chinzei R, Shimizu-Saito K, Tanaka Y, Teraoka H, Arii S. Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells. J Hepatobiliary Pancreat Surg 2005; 12: 196-202 [PMID: 15995807].
64. Chien CC, Yen BL, Lee FK, Lai TH, Chen YC, Chan SH, Huang HI. In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells. Stem Cells 2006; 24: 1759-1768 [PMID: 16822884].
65. Huang HI. Isolation of human placenta-derived multipotent cells and in vitro differentiation into hepatocyte-like cells. Curr Protoc Stem Cell Biol 2007; Chapter 1: Unit 1E.1 [PMID: 18785166 DOI:10.1002/9780470151808.sc01e01s1].
66. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 6: 1229-1234 [PMID: 11062533].
67. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284: 1168-1170 [PMID: 10325227].
68. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-705 [PMID: 11287958].
69. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528-1530 [PMID: 9488650].
70. Brazelton TR, Rossi FM, Keshet GI, Blau HM. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000; 290: 1775-1779 [PMID: 11099418].
71. Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003; 111: 843-850 [PMID: 12639990].
72. 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].
73. Nakamura T, Torimura T, Sakamoto M, Hashimoto O, Taniguchi E, Inoue K, Sakata R, Kumashiro R, Murohara T, Ueno T, Sata M. Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model. Gastroenterology 2007; 133: 91-107.e1 [PMID: 17631135].
74. Wang L, Wang X, Xie G, Wang L, Hill CK, DeLeve LD. Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats. J Clin Invest 2012; 122: 1567-1573 [PMID: 22406533 DOI:10.1172/JCI58789].
75. Ueno T, Nakamura T, Torimura T, Sata M. Angiogenic cell therapy for hepatic fibrosis. Med Mol Morphol 2006; 39: 16-21 [PMID: 16575510].
76. Taniguchi E, Kin M, Torimura T, Nakamura T, Kumemura H, Hanada S, Hisamoto T, Yoshida T, Kawaguchi T, Baba S, Maeyama M, Koga H, Harada M, Kumashiro R, Ueno T, Mizuno S, Ikeda H, Imaizumi T, Murohara T, Sata M. Endothelial progenitor cell transplantation improves the survival following liver injury in mice. Gastroenterology 2006; 130: 521-531 [PMID: 16472604].
77. Beaudry P, Hida Y, Udagawa T, Alwayn IP, Greene AK, Arsenault D, Folkman J, Heymach JV, Ryeom S, Puder M. Endothelial progenitor cells contribute to accelerated liver regeneration. J Pediatr Surg 2007; 42: 1190-1198 [PMID: 17618879].
78. 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].
79. 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].
80. Sottile V, Halleux C, Bassilana F, Keller H, Seuwen K. Stem cell characteristics of human trabecular bone-derived cells. Bone 2002; 30: 699-704 [PMID: 11996907].
81. De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001; 44: 1928-1942 [PMID: 11508446].
82. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13: 4279-4295 [PMID: 12475952].
83. Intanker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GM, Claas FH, Fibbe WE, Kanhai HH. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004; 22: 1338-1345 [PMID: 15579651].
84. In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE, Kanhai HH. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003; 102: 1548-1549 [PMID: 12900350].
85. intanker 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].
86. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007; 110: 3499-3506 [PMID: 17664353].
87. El-Badri NS, Maheshwari A, Sanberg PR. Mesenchymal stem cells in autoimmune disease. Stem Cells Dev 2004; 13: 463-472 [PMID: 15588504].
88. Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81: 1390-1397 [PMID: 16732175].
89. Bunnell BA, Deng W, Robinson CM, Waldron PR, Bivalacqua TJ, Baber SR, Hyman AL, Kadowitz PJ. Potential application for mesenchymal stem cells in the treatment of cardiovascular diseases. Can J Physiol Pharmacol 2005; 83: 529-539 [PMID: 16091779].
90. Minguell JJ, Erices A. Mesenchymal stem cells and the treatment of cardiac disease. Exp Biol Med (Maywood) 2006; 231: 39-49 [PMID: 16380643].
91. McTaggart SJ, Atkinson K. Mesenchymal stem cells: immunobiology and therapeutic potential in kidney disease. Nephrology (Carlton) 2007; 12: 44-52 [PMID: 17295660].
92. 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].
93. Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR, Fiegel HC. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells. World J Gastroenterol 2005; 11: 4497-4504 [PMID: 16052678].
94. Luk JM, Wang PP, Lee CK, Wang JH, Fan ST. Hepatic potential of bone marrow stromal cells: development of in vitro co-culture and intra-portal transplantation models. J Immunol Methods 2005; 305: 39-47 [PMID: 16150456].
95. Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004; 40: 1275-1284 [PMID: 15562440].
96. 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 [PMID: 15670778].
97. Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kato T, Okochi H, Ochiya T. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol 2009; 24: 70-77 [PMID: 18624899 DOI:10.1111/j.1440-1746.2008.05496.x].
98. Zheng YB, Gao ZL, Xie C, Zhu HP, Peng L, Chen JH, Chong YT. Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: A comparative study. Cell Biol Int 2008; 32: 1439-1448 [PMID: 18782626 DOI:10.1016/j.cellbi.2008.08.015].
99. Ishkitiev N, Yaegaki K, Calenic B, Nakahara T, Ishikawa H, Mitiev V, Haapasalo M. Deciduous and permanent dental pulp mesenchymal cells acquire hepatic morphologic and functional features in vitro. J Endod 2010; 36: 469-474 [PMID: 20171365 DOI:10.1016/j.joen.2009.12.022].
100. Ling L, Ni Y, Wang Q, Wang H, Hao S, Hu Y, Jiang W, Hou Y. Transdifferentiation of mesenchymal stem cells derived from human fetal lung to hepatocyte-like cells. Cell Biol Int 2008; 32: 1091-1098 [PMID: 18572423 DOI:10.1016/j.cellbi.2008.04.020].
101. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24: 1294-1301 [PMID: 16410387].
102. Zhu X, He B, Zhou X, Ren J. Effects of transplanted bonemarrow- derived mesenchymal stem cells in animal models of acute hepatitis. Cell Tissue Res 2013; 351: 477-486 [PMID: 23143676 DOI:10.1007/s00441-012-1524-3].
103. Cho KA, Ju SY, Cho SJ, Jung YJ, Woo SY, Seoh JY, Han HS, Ryu KH. Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow. Cell Biol Int 2009; 33: 772-777 [PMID: 19427913 DOI:10.1016/j.cellbi.2009.04.023].
104. Cao H, Yang J, Yu J, Pan Q, Li J, Zhou P, Li Y, Pan X, Li J, Wang Y, Li L. Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure. BMC Med 2012; 10: 56 [PMID: 22673529 DOI:10.1186/1741-7015-10-56].
105. Pascual-Miguelañez I, Salinas-Gomez J, Fernandez-Luengas D, Villar-Zarra K, Clemente LV, Garcia-Arranz M, Olmo DG. Systemic treatment of acute liver failure with adipose derived stem cells. J Invest Surg 2015; 28: 120-126 [PMID: 25517764 DOI:10.3109/08941939.2014.987407].
106. 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 [PMID: 23954692 DOI:10.1016/j.scr.2013.07.003].
107. Manzini BM, da Silva Santos Duarte A, Sankaramanivel S, Ramos AL, Latuf-Filho P, Escanhoela C, Kharmandayan P, Olalla Saad ST, Boin I, Malheiros Luzo ÂC. Useful properties of undifferentiated mesenchymal stromal cells and adipose tissue as the source in liver-regenerative therapy studied in an animal model of severe acute fulminant hepatitis. Cytotherapy 2015; 17: 1052-1065 [PMID: 26139545 DOI:10.1016/j.jcyt.2015.04.010].
108. 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].
109. Li J, Zhang L, Xin J, Jiang L, Li J, Zhang T, Jin L, Li J, Zhou P, Hao S, Cao H, Li L. Immediate intraportal transplantation of human bone marrow mesenchymal stem cells prevents death from fulminant hepatic failure in pigs. Hepatology 2012; 56: 1044-1052 [PMID: 22422600 DOI:10.1002/hep.25722].
110. Xin J, Ding W, Hao S, Jiang L, Zhou Q, Wu T, Shi D, Cao H, Li L, Li J. Human bone marrow mesenchymal stem cell-derived hepatocytes express tissue inhibitor of metalloproteinases 4 and follistatin. Liver Int 2015; 35: 2301-2310 [PMID: 25645195 DOI:10.1111/liv.12797].
111. Xagorari A, Siotou E, Yiangou M, Tsolaki E, Bougiouklis D, Sakkas L, Fassas A, Anagnostopoulos A. Protective effect of mesenchymal stem cell-conditioned medium on hepatic cell apoptosis after acute liver injury. Int J Clin Exp Pathol 2013; 6: 831-840 [PMID: 23638214].
112. 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].
113. 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].
114. Zagoura DS, Roubelakis MG, Bitsika V, Trohatou O, Pappa KI, Kapelouzou A, Antsaklis A, Anagnou NP. 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 [PMID: 21997562 DOI:10.1136/gutjnl-2011-300908].
115. Zhang S, Chen L, Liu T, Zhang B, Xiang D, Wang Z, Wang Y. Human umbilical cord matrix stem cells efficiently rescue acute liver failure through paracrine effects rather than hepatic differentiation. Tissue Eng Part A 2012; 18: 1352-1364 [PMID: 22519429 DOI:10.1089/ten.TEA.2011.0516].
116. Yuan S, Jiang T, Zheng R, Sun L, Cao G, Zhang Y. Effect of bone marrow mesenchymal stem cell transplantation on acute hepatic failure in rats. Exp Ther Med 2014; 8: 1150-1158 [PMID: 25187814].
117. Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao RC. Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation 2004; 78: 83-88 [PMID: 15257043].
118. Zhao DC, Lei JX, Chen R, Yu WH, Zhang XM, Li SN, Xiang P. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol 2005; 11: 3431-3440 [PMID: 15948250].
119. Jang YO, Kim MY, Cho MY, Baik SK, Cho YZ, Kwon SO. Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model. BMC Gastroenterol 2014; 14: 198 [PMID: 25425284 DOI:10.1186/s12876-014-0198-6].
120. Yu F, Ji S, Su L, Wan L, Zhang S, Dai C, Wang Y, Fu J, Zhang Q. Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo. J Formos Med Assoc 2015; 114: 130-138 [PMID: 25678175 DOI:10.1016/j.jfma.2012.12.002].
121. 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].
122. 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].
123. Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T, Brulport M, Hengstler JG, Dollinger MM, Fleig WE, Christ B. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 2009; 58: 570-581 [PMID: 19022918 DOI:10.1136/gut.2008.154880].
124. Kamada Y, Yoshida Y, Saji Y, Fukushima J, Tamura S, Kiso S, Hayashi N. Transplantation of basic fibroblast growth factorpretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice. Am J Physiol Gastrointest Liver Physiol 2009; 296: G157-G167 [PMID: 19056764 DOI:10.1152/ajpgi.90463.2008].
125. Tang WP, Akahoshi T, Piao JS, Narahara S, Murata M, Kawano T, Hamano N, Ikeda T, Hashizume M. Basic fibroblast growth factortreated adipose tissue-derived mesenchymal stem cell infusion to ameliorate liver cirrhosis via paracrine hepatocyte growth factor. J Gastroenterol Hepatol 2015; 30: 1065-1074 [PMID: 25639333 DOI:10.1111/jgh.12893].
126. Shams S, Mohsin S, Nasir GA, Khan M, Khan SN. Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice. Stem Cells Int 2015; 2015: 747245 [PMID: 25685159 DOI:10.1155/2015/747245].
127. Mohsin S, Shams S, Ali Nasir G, Khan M, Javaid Awan S, Khan SN, Riazuddin S. Enhanced hepatic differentiation of mesenchymal stem cells after pretreatment with injured liver tissue. Differentiation 2011; 81: 42-48 [PMID: 20943307 DOI:10.1016/j.diff.2010.08.005].
128. 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].
129. 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 [PMID: 16469408].
130. 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].
131. Li T, Zhu J, Ma K, Liu N, Feng K, Li X, Wang S, Bie P. Autologous bone marrow-derived mesenchymal stem cell transplantation promotes liver regeneration after portal vein embolization in cirrhotic rats. J Surg Res 2013; 184: 1161-1173 [PMID: 23809154 DOI:10.1016/j.jss.2013.04.054].
132. Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H. Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int 2010; 34: 601-605 [PMID: 20178458 DOI:10.1042/CBI20090386].
133. 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].
134. 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].
135. Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol 2011; 23: 936-941 [PMID: 21900788 DOI:10.1097/MEG.0b013e3283488b00].
136. 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: shortterm and long-term outcomes. Hepatology 2011; 54: 820-828 [PMID: 21608000 DOI:10.1002/hep.24434].
137. 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].
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. 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].
140. 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].
141. 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].
142. 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].
143. Mohamadnejad M, Alimoghaddam K, Bagheri M, Ashrafi M, Abdollahzadeh L, Akhlaghpoor S, Bashtar M, Ghavamzadeh A, Malekzadeh R. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int 2013; 33: 1490-1496 [PMID: 23763455 DOI:10.1111/liv.12228].
144. 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].
145. 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].
146. Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamante O, Segovia JC, Schwabe RF, Brenner DA. Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol 2006; 45: 429-438 [PMID: 16846660].
147. Meier RP, Mahou R, Morel P, Meyer J, Montanari E, Muller YD, Christofilopoulos P, Wandrey C, Gonelle-Gispert C, Bühler LH. Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice. J Hepatol 2015; 62: 634-641 [PMID: 25450712 DOI:10.1016/j.jhep.2014.10.030].
148. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noël D, Jorgensen C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102: 3837-3844 [PMID: 12881305].
149. Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C, Chen Y. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol 2006; 80: 267-274 [PMID: 16214129].
150. Yu JM, Jun ES, Bae YC, Jung JS. Mesenchymal stem cells derived from human adipose tissues favor tumor cell growth in vivo. Stem Cells Dev 2008; 17: 463-473 [PMID: 18522494 DOI:10.1089/scd.2007.0181].
151. Pan Q, Fouraschen SM, de Ruiter PE, Dinjens WN, Kwekkeboom J, Tilanus HW, van der Laan LJ. Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells. Exp Biol Med (Maywood) 2014; 239: 105-115 [PMID: 24227633 DOI:10.1177/1535370213506802].
152. Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II, Nguyen AT, Malide D, Combs CA, Hall G, Zhang J, Raffeld M, Rogers TB, Stetler-Stevenson W, Frank JA, Reitz M, Finkel T. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med 2006; 203: 1235-1247 [PMID: 16636132].
153. Qiao L, Xu Z, Zhao T, Zhao Z, Shi M, Zhao RC, Ye L, Zhang X. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res 2008; 18: 500-507 [PMID: 18364678 DOI:10.1038/cr.2008.40].
154. Lu YR, Yuan Y, Wang XJ, Wei LL, Chen YN, Cong C, Li SF, Long D, Tan WD, Mao YQ, Zhang J, Li YP, Cheng JQ. The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo. Cancer Biol Ther 2008; 7: 245-251 [PMID: 18059192].
155. Gao P, Ding Q, Wu Z, Jiang H, Fang Z. Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma. Cancer Lett 2010; 290: 157-166 [PMID: 19786319 DOI:10.1016/j.canlet.2009.08.031].
156. Abdel aziz MT, El Asmar MF, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Rashed LA, Sabry D, Hassouna AA, Taha FM. Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling. J Exp Clin Cancer Res 2011; 30: 49 [PMID: 21545718 DOI:10.1186/1756-9966-30-49].
157. 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].
158. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS. Liver from bone marrow in humans. Hepatology 2000; 32: 11-16 [PMID: 10869283].
159. De Silvestro G, Vicarioto M, Donadel C, Menegazzo M, Marson P, Corsini A. Mobilization of peripheral blood hematopoietic stem cells following liver resection surgery. Hepatogastroenterology 2004; 51: 805-810 [PMID: 15143921].
160. Gehling UM, Willems M, Dandri M, Petersen J, Berna M, Thill M, Wulf T, Müller L, Pollok JM, Schlagner K, Faltz C, Hossfeld DK, Rogiers X. Partial hepatectomy induces mobilization of a unique population of haematopoietic progenitor cells in human healthy liver donors. J Hepatol 2005; 43: 845-853 [PMID: 16139387].
161. Gehling UM, Willems M, Schlagner K, Benndorf RA, Dandri M, Petersen J, Sterneck M, Pollok JM, Hossfeld DK, Rogiers X. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis. World J Gastroenterol 2010; 16: 217-224 [PMID: 20066741].
162. Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, Okita K. Transplantation of bone marrow cells reduces CCl4- induced liver fibrosis in mice. Hepatology 2004; 40: 1304-1311 [PMID: 15565662].
163. Thomas JA, Pope C, Wojtacha D, Robson AJ, Gordon-Walker TT, Hartland S, Ramachandran P, Van Deemter M, Hume DA, Iredale JP, Forbes SJ. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology 2011; 53: 2003-2015 [PMID: 21433043 DOI:10.1002/hep.24315].
164. 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].
165. Fürst G, Schulte am Esch J, Poll LW, Hosch SB, Fritz LB, Klein M, Godehardt E, Krieg A, Wecker B, Stoldt V, Stockschläder M, Eisenberger CF, Mödder U, Knoefel WT. Portal vein embolization and autologous CD133+ bone marrow stem cells for liver regeneration: initial experience. Radiology 2007; 243: 171-179 [PMID: 17312278].
166. Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 2006; 24: 2292-2298 [PMID: 16778155].
167. Lemoli RM, Catani L, Talarico S, Loggi E, Gramenzi A, Baccarani U, Fogli M, Grazi GL, Aluigi M, Marzocchi G, Bernardi M, Pinna A, Bresadola F, Baccarani M, Andreone P. Mobilization of bone marrow-derived hematopoietic and endothelial stem cells after orthotopic liver transplantation and liver resection. Stem Cells 2006; 24: 2817-2825 [PMID: 16931769].
168. To LB, Haylock DN, Simmons PJ, Juttner CA. The biology and clinical uses of blood stem cells. Blood 1997; 89: 2233-2258 [PMID: 9116266].
169. Mohty M, Ho AD. In and out of the niche: perspectives in mobilization of hematopoietic stem cells. Exp Hematol 2011; 39: 723-729 [PMID: 21624427 DOI:10.1016/j.exphem.2011.05.004].
170. Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 1989; 339: 27-30 [PMID: 2469962].
171. Yannaki E, Athanasiou E, Xagorari A, Constantinou V, Batsis I, Kaloyannidis P, Proya E, Anagnostopoulos A, Fassas A. G-CSFprimed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol 2005; 33: 108-119 [PMID: 15661404].
172. Quintana-Bustamante O, Alvarez-Barrientos A, Kofman AV, Fabregat I, Bueren JA, Theise ND, Segovia JC. Hematopoietic mobilization in mice increases the presence of bone marrowderived hepatocytes via in vivo cell fusion. Hepatology 2006; 43: 108-116 [PMID: 16374873].
173. Piscaglia AC, Shupe TD, Oh SH, Gasbarrini A, Petersen BE. Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats. Gastroenterology 2007; 133: 619-631 [PMID: 17681181].
174. Tsolaki E, Athanasiou E, Gounari E, Zogas N, Siotou E, Yiangou M, Anagnostopoulos A, Yannaki E. Hematopoietic stem cells and liver regeneration: differentially acting hematopoietic stem cell mobilization agents reverse induced chronic liver injury. Blood Cells Mol Dis 2014; 53: 124-132 [PMID: 24923531 DOI:10.1016/j.bcmd.2014.05.003].
175. Gaia S, Smedile A, Omedè P, Olivero A, Sanavio F, Balzola F, Ottobrelli A, Abate ML, Marzano A, Rizzetto M, Tarella C. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol 2006; 45: 13-19 [PMID: 16635534].
176. Yannaki E, Anagnostopoulos A, Kapetanos D, Xagorari A, Iordanidis F, Batsis I, Kaloyannidis P, Athanasiou E, Dourvas G, Kitis G, Fassas A. Lasting amelioration in the clinical course of decompensated alcoholic cirrhosis with boost infusions of mobilized peripheral blood stem cells. Exp Hematol 2006; 34: 1583-1587 [PMID: 17046578].
177. Gordon MY, Levicar N, Pai M, Bachellier P, Dimarakis I, Al-Allaf F, M'Hamdi H, Thalji T, Welsh JP, Marley SB, Davies J, Dazzi F, Marelli-Berg F, Tait P, Playford R, Jiao L, Jensen S, Nicholls JP, Ayav A, Nohandani M, Farzaneh F, Gaken J, Dodge R, Alison M, Apperley JF, Lechler R, Habib NA. 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 [PMID: 16556705].
178. Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: A randomized trial. Hepatology 2008; 48: 221-229 [PMID: 18537187 DOI:10.1002/hep.22317].
179. Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012; 142: 505-512.e1 [PMID: 22119930 DOI:10.1053/j.gastro.2011.11.027].
180. Singh V, Sharma AK, Narasimhan RL, Bhalla A, Sharma N, Sharma R. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: A randomized pilot study. Am J Gastroenterol 2014; 109: 1417-1423 [PMID: 24935272 DOI:10.1038/ajg.2014.154].
181. Piscaglia AC, Arena V, Passalacqua S, Gasbarrini A. A case of granulocyte-colony stimulating factor/plasmapheresis-induced activation of granulocyte-colony stimulating factor-positive hepatic progenitors in acute-on-chronic liver failure. Hepatology 2015; 62: 649-652 [PMID: 25644621 DOI:10.1002/hep.27708].
182. Di Campli C, Zocco MA, Saulnier N, Grieco A, Rapaccini G, Addolorato G, Rumi C, Santoliquido A, Leone G, Gasbarrini G, Gasbarrini A. Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure. Dig Liver Dis 2007; 39: 1071-1076 [PMID: 17964871].
183. Lorenzini S, Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M, Bernardi M, Forbes SJ, Lemoli RM, Andreone P. Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther 2008; 27: 932-939 [PMID: 18315586 DOI:10.1111/j.1365-2036.2008.03670.x].
184. Gasbarrini A, Rapaccini GL, Rutella S, Zocco MA, Tittoto P, Leone G, Pola P, Gasbarrini G, Di Campli C. Rescue therapy by portal infusion of autologous stem cells in a case of drug-induced hepatitis. Dig Liver Dis 2007; 39: 878-882 [PMID: 16875890].
185. Levicar N, Pai M, Habib NA, Tait P, Jiao LR, Marley SB, Davis J, Dazzi F, Smadja C, Jensen SL, Nicholls JP, Apperley JF, Gordon MY. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif 2008; 41 Suppl 1: 115-125 [PMID: 18181952 DOI:10.1111/j.1365-2184.2008.00491.x].
186. Pai M, Zacharoulis D, Milicevic MN, Helmy S, Jiao LR, Levicar N, Tait P, Scott M, Marley SB, Jestice K, Glibetic M, Bansi D, Khan SA, Kyriakou D, Rountas C, Thillainayagam A, Nicholls JP, Jensen S, Apperley JF, Gordon MY, Habib NA. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol 2008; 103: 1952-1958 [PMID: 18637092 DOI:10.1111/j.1572-0241.2008.01993.x].
187. Han Y, Yan L, Han G, Zhou X, Hong L, Yin Z, Zhang X, Wang S, Wang J, Sun A, Liu Z, Xie H, Wu K, Ding J, Fan D. Controlled trials in hepatitis B virus-related decompensate liver cirrhosis: peripheral blood monocyte transplant versus granulocyte-colonystimulating factor mobilization therapy. Cytotherapy 2008; 10: 390-396 [PMID: 18574771 DOI:10.1080/14653240802129901].
188. Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut 2007; 56: 716-724 [PMID: 17145739].
189. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297: 2256-2259 [PMID: 12215650].
190. Thorgeirsson SS, Grisham JW. Hematopoietic cells as hepatocyte stem cells: A critical review of the evidence. Hepatology 2006; 43: 2-8 [PMID: 16374844].
191. Loffredo FS, Steinhauser ML, Gannon J, Lee RT. Bone marrowderived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell 2011; 8: 389-398 [PMID: 21474103 DOI:10.1016/j.stem.2011.02.002].
192. Tang XL, Rokosh G, Sanganalmath SK, Yuan F, Sato H, Mu J, Dai S, Li C, Chen N, Peng Y, Dawn B, Hunt G, Leri A, Kajstura J, Tiwari S, Shirk G, Anversa P, Bolli R. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation 2010; 121: 293-305 [PMID: 20048209 DOI:10.1161/CIRCULATIONAHA.109.871905].
193. 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].
194. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422: 901-904 [PMID: 12665833].
195. Lin N, Lin J, Bo L, Weidong P, Chen S, Xu R. Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells in an alginate scaffold. Cell Prolif 2010; 43: 427-434 [PMID: 20887549 DOI:10.1111/j.1365-2184.2010.00692.x].
196. Kazemnejad S, Allameh A, Soleimani M, Gharehbaghian A, Mohammadi Y, Amirizadeh N, Jazayery M. Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel threedimensional biocompatible nanofibrous scaffold. J Gastroenterol Hepatol 2009; 24: 278-287 [PMID: 18752558 DOI:10.1111/j.1440-1746.2008.05530.x].
197. 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].
198. Li J, Tao R, Wu W, Cao H, Xin J, Li J, Guo J, Jiang L, Gao C, Demetriou AA, Farkas DL, Li L. 3D PLGA scaffolds improve differentiation and function of bone marrow mesenchymal stem cell-derived hepatocytes. Stem Cells Dev 2010; 19: 1427-1436 [PMID: 20055663 DOI:10.1089/scd.2009.0415].
199. Li P, Zhang J, Liu J, Ma H, Liu J, Lie P, Wang Y, Liu G, Zeng H, Li Z, Wei X. Promoting the recovery of injured liver with poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) scaffolds loaded with umbilical cord-derived mesenchymal stem cells. Tissue Eng Part A 2015; 21: 603-615 [PMID: 25273546 DOI:10.1089/ten.TEA.2013.0331].
200. Soto-Gutiérrez A, Kobayashi N, Rivas-Carrillo JD, Navarro- Alvarez N, Zhao D, Okitsu T, Noguchi H, Basma H, Tabata Y, Chen Y, Tanaka K, Narushima M, Miki A, Ueda T, Jun HS, Yoon JW, Lebkowski J, Tanaka N, Fox IJ. Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cellderived hepatocytes. Nat Biotechnol 2006; 24: 1412-1419 [PMID: 17086173].
201. Chia HN, Wu BM. Recent advances in 3D printing of biomaterials. J Biol Eng 2015; 9: 4 [PMID: 25866560 DOI:10.1186/s13036-015-0001-4].
202. Li YS, Harn HJ, Hsieh DK, Wen TC, Subeq YM, Sun LY, Lin SZ, Chiou TW. Cells and materials for liver tissue engineering. Cell Transplant 2013; 22: 685-700 [PMID: 23127824 DOI:10.3727/096368912X655163].