Therapeutic potential of stem cell in liver regeneration
Jinzheng LI, Min LI, Bolin NIU, Jianping GONG
Therapeutic potential of stem cell in liver regeneration
Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.
stem cell / liver disease / regenerative medicine
[1] |
O’Leary J G, Lepe R, Davis G L. Indications for liver transplantation. Gastroenterology, 2008, 134(6): 1764-1776
CrossRef
Pubmed
Google scholar
|
[2] |
Kung J W, Forbes S J. Stem cells and liver repair. Curr Opin Biotechnol, 2009, 20(5): 568-574
CrossRef
Pubmed
Google scholar
|
[3] |
Ogawa S, Miyagawa S. Potentials of regenerative medicine for liver disease. Surg Today, 2009, 39(12): 1019-1025
CrossRef
Pubmed
Google scholar
|
[4] |
Ehnert S, Glanemann M, Schmitt A, Vogt S, Shanny N, Nussler N C, Stöckle U, Nussler A. The possible use of stem cells in regenerative medicine: dream or reality? Langenbecks Arch Surg, 2009, 394(6): 985-997
CrossRef
Pubmed
Google scholar
|
[5] |
Alison M R, Islam S, Lim S. Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly. J Pathol, 2009, 217(2): 282-298
CrossRef
Pubmed
Google scholar
|
[6] |
Fausto N, Campbell J S, Riehle K J. Liver regeneration. Hepatology, 2006, 43 (Suppl 1): S45-S53
CrossRef
Pubmed
Google scholar
|
[7] |
Roskams T A, Theise N D, Balabaud C, Bhagat G, Bhathal P S, Bioulac-Sage P, Brunt E M, Crawford J M, Crosby H A, Desmet V, Finegold M J, Geller S A, Gouw A S, Hytiroglou P, Knisely A S, Kojiro M, Lefkowitch J H, Nakanuma Y, Olynyk J K, Park Y N, Portmann B, Saxena R, Scheuer P J, Strain A J, Thung S N, Wanless I R, West A B. Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology, 2004, 39(6): 1739-1745
CrossRef
Pubmed
Google scholar
|
[8] |
Dorrell C, Grompe M. Liver repair by intra- and extrahepatic progenitors. Stem Cell Rev, 2005, 1(1): 61-64
CrossRef
Pubmed
Google scholar
|
[9] |
Lee J S, Heo J, Libbrecht L, Chu I S, Kaposi-Novak P, Calvisi D F, Mikaelyan A, Roberts L R, Demetris A J, Sun Z, Nevens F, Roskams T, Thorgeirsson S S. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med, 2006, 12(4): 410-416
CrossRef
Pubmed
Google scholar
|
[10] |
Tanaka M, Okabe M, Suzuki K, Kamiya Y, Tsukahara Y, Saito S, Miyajima A. Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: drastic change of EpCAM expression during liver development. Mech Dev, 2009, 126(8-9): 665-676
CrossRef
Pubmed
Google scholar
|
[11] |
Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, Tsujimura T, Nakamura K, Miyajima A. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development, 2009, 136(11): 1951-1960
CrossRef
Pubmed
Google scholar
|
[12] |
Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao H L, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth M E, Reid L M. Human hepatic stem cells from fetal and postnatal donors. J Exp Med, 2007, 204(8): 1973-1987
CrossRef
Pubmed
Google scholar
|
[13] |
Sangan C B, Tosh D. Hepatic progenitor cells. Cell Tissue Res, 2010, 342(2): 131-137
CrossRef
Pubmed
Google scholar
|
[14] |
Oertel M, Menthena A, Dabeva M D, Shafritz D A. Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology, 2006, 130(2): 507-520
CrossRef
Pubmed
Google scholar
|
[15] |
Oertel M, Menthena A, Chen Y Q, Teisner B, Jensen C H, Shafritz D A. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver. Gastroenterology, 2008, 134(3): 823-832
Pubmed
|
[16] |
Mahieu-Caputo D, Allain J E, Branger J, Coulomb A, Delgado J P, Andreoletti M, Mainot S, Frydman R, Leboulch P, Di Santo J P, Capron F, Weber A. Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts. Hum Gene Ther, 2004, 15(12): 1219-1228
CrossRef
Pubmed
Google scholar
|
[17] |
Kallis Y N, Alison M R, Forbes S J. Bone marrow stem cells and liver disease. Gut, 2007, 56(5): 716-724
CrossRef
Pubmed
Google scholar
|
[18] |
Petersen B E, Bowen W C, Patrene K D, Mars W M, Sullivan A K, Murase N, Boggs S S, Greenberger J S, Goff J P. Bone marrow as a potential source of hepatic oval cells. Science, 1999, 284(5417): 1168-1170
CrossRef
Pubmed
Google scholar
|
[19] |
Gilchrist E S, Plevris J N. Bone marrow-derived stem cells in liver repair: 10 years down the line. Liver Transpl, 2010, 16(2): 118-129
CrossRef
Pubmed
Google scholar
|
[20] |
Houlihan D D, Newsome P N. Critical review of clinical trials of bone marrow stem cells in liver disease. Gastroenterology, 2008, 135(2): 438-450
CrossRef
Pubmed
Google scholar
|
[21] |
Levicar N, Pai M, Habib N A, Tait P, Jiao L R, Marley S B, Davis J, Dazzi F, Smadja C, Jensen S L, Nicholls J P, Apperley J F, Gordon M Y. 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
CrossRef
Pubmed
Google scholar
|
[22] |
Tajima F, Tsuchiya H, Nishikawa K, Kataoka M, Hisatome I, Shiota G. Hepatocyte growth factor mobilizes and recruits hematopoietic progenitor cells into liver through a stem cell factor-mediated mechanism. Hepatol Res, 2010, 40(7): 711-719
CrossRef
Pubmed
Google scholar
|
[23] |
Yamaguchi K, Itoh K, Masuda T, Umemura A, Baum C, Itoh Y, Okanoue T, Fujita J. In vivo selection of transduced hematopoietic stem cells and little evidence of their conversion into hepatocytes in vivo. J Hepatol, 2006, 45(5): 681-687
CrossRef
Pubmed
Google scholar
|
[24] |
Friedenstein A J, Chailakhjan R K, Lalykina K S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet, 1970, 3(4): 393-403
Pubmed
|
[25] |
Lee K D, Kuo T K, Whang-Peng J, Chung Y F, Lin C T, Chou S H, Chen J R, Chen Y P, Lee O K. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology, 2004, 40(6): 1275-1284
CrossRef
Pubmed
Google scholar
|
[26] |
Liu Z J, Zhuge Y, Velazquez O C. Trafficking and differentiation of mesenchymal stem cells. J Cell Biochem, 2009, 106(6): 984-991
CrossRef
Pubmed
Google scholar
|
[27] |
Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T, Brulport M, Hengstler J G, Dollinger M M, Fleig W E, Christ B. Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut, 2009, 58(4): 570-581
CrossRef
Pubmed
Google scholar
|
[28] |
Cho K A, Ju S Y, Cho S J, Jung Y J, Woo S Y, Seoh J Y, Han H S, Ryu K H. 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(7): 772-777
CrossRef
Pubmed
Google scholar
|
[29] |
Kuo T K, Hung S P, Chuang C H, Chen C T, Shih Y R, Fang S C, Yang V W, Lee O K. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology, 2008; 134(7):2111-2121, 2121.e1-3
|
[30] |
Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology, 2007, 46(1): 219-228
CrossRef
Pubmed
Google scholar
|
[31] |
Wang Z, Lu H, Wang Y C, Cong X Q. Human embryonic stem cells and liver diseases: from basic research to future clinical application. J Dig Dis, 2008, 9(1): 14-19
CrossRef
Pubmed
Google scholar
|
[32] |
Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, Meng S, Chen Y, Zhou R, Song X, Guo Y, Ding M, Deng H. Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology, 2007, 45(5): 1229-1239
CrossRef
Pubmed
Google scholar
|
[33] |
Dan Y Y, Yeoh G C. Liver stem cells: a scientific and clinical perspective. J Gastroenterol Hepatol, 2008, 23(5): 687-698
CrossRef
Pubmed
Google scholar
|
[34] |
Dalgetty D M, Medine C N, Iredale J P, Hay D C. Progress and future challenges in stem cell-derived liver technologies. Am J Physiol Gastrointest Liver Physiol, 2009, 297(2): G241-G248
CrossRef
Pubmed
Google scholar
|
[35] |
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4): 663-676
CrossRef
Pubmed
Google scholar
|
[36] |
Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature, 2007, 448(7151): 313-317
CrossRef
Pubmed
Google scholar
|
[37] |
Yu J, Vodyanik M A, Smuga-Otto K, Antosiewicz-Bourget J, Frane J L, Tian S, Nie J, Jonsdottir G A, Ruotti V, Stewart R, Slukvin I I, Thomson J A. Induced pluripotent stem cell lines derived from human somatic cells. Science, 2007, 318(5858): 1917-1920
CrossRef
Pubmed
Google scholar
|
[38] |
Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein B E, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 2007, 448(7151): 318-324
CrossRef
Pubmed
Google scholar
|
[39] |
Lowry W E, Richter L, Yachechko R, Pyle A D, Tchieu J, Sridharan R, Clark A T, Plath K. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA, 2008, 105(8): 2883-2888
CrossRef
Pubmed
Google scholar
|
[40] |
Park I H, Zhao R, West J A, Yabuuchi A, Huo H, Ince T A, Lerou P H, Lensch M W, Daley G Q. Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 2008, 451(7175): 141-146
CrossRef
Pubmed
Google scholar
|
[41] |
Kim J B, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo M J, Ruau D, Han D W, Zenke M, Schöler H R. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 2008, 454(7204): 646-650
CrossRef
Pubmed
Google scholar
|
[42] |
Carey B W, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, Jaenisch R. Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci USA, 2009, 106(1): 157-162
CrossRef
Pubmed
Google scholar
|
[43] |
Li W, Wei W, Zhu S, Zhu J, Shi Y, Lin T, Hao E, Hayek A, Deng H, Ding S. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell, 2009, 4(1): 16-19
CrossRef
Pubmed
Google scholar
|
[44] |
Theise N D, Nimmakayalu M, Gardner R, Illei P B, Morgan G, Teperman L, Henegariu O, Krause D S. Liver from bone marrow in humans. Hepatology, 2000, 32(1): 11-16
CrossRef
Pubmed
Google scholar
|
[45] |
Alison M R, Poulsom R, Jeffery R, Dhillon A P, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright N A. Hepatocytes from non-hepatic adult stem cells. Nature, 2000, 406(6793): 257
CrossRef
Pubmed
Google scholar
|
[46] |
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(2): 756-763
CrossRef
Pubmed
Google scholar
|
[47] |
Jang Y Y, Collector M I, Baylin S B, Diehl A M, Sharkis S J. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol, 2004, 6(6): 532-539
CrossRef
Pubmed
Google scholar
|
[48] |
Willenbring H, Bailey A S, Foster M, Akkari Y, Dorrell C, Olson S, Finegold M, Fleming W H, Grompe M. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat Med, 2004, 10(7): 744-748
CrossRef
Pubmed
Google scholar
|
[49] |
Quintana-Bustamante O, Alvarez-Barrientos A, Kofman A V, Fabregat I, Bueren J A, Theise N D, Segovia J C. Hematopoietic mobilization in mice increases the presence of bone marrow-derived hepatocytes via in vivo cell fusion. Hepatology, 2006, 43(1): 108-116
CrossRef
Pubmed
Google scholar
|
[50] |
Rodić N, Rutenberg M S, Terada N. Cell fusion and reprogramming: resolving our transdifferences. Trends Mol Med, 2004, 10(3): 93-96
CrossRef
Pubmed
Google scholar
|
[51] |
Dahlke M H, Popp F C, Larsen S, Schlitt H J, Rasko J E. Stem cell therapy of the liver—fusion or fiction? Liver Transpl, 2004, 10(4): 471-479
CrossRef
Pubmed
Google scholar
|
[52] |
Camargo F D, Finegold M, Goodell M A. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J Clin Invest, 2004, 113(9): 1266-1270
Pubmed
|
[53] |
Krause P, Saghatolislam F, Koenig S, Unthan-Fechner K, Probst I. Maintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells. In Vitro Cell Dev Biol Anim, 2009, 45(5-6): 205-212
CrossRef
Pubmed
Google scholar
|
[54] |
Woodrow K A, Wood M J, Saucier-Sawyer J K, Solbrig C, Saltzman W M. Biodegradable meshes printed with extracellular matrix proteins support micropatterned hepatocyte cultures. Tissue Eng Part A, 2009, 15(5): 1169-1179
CrossRef
Pubmed
Google scholar
|
[55] |
Wen F, Chang S, Toh Y C, Arooz T, Zhuo L, Teoh S H, Yu H. Development of dual-compartment perfusion bioreactor for serial coculture of hepatocytes and stellate cells in poly(lactic-co-glycolic acid)-collagen scaffolds. J Biomed Mater Res B Appl Biomater, 2008, 87(1): 154-162
CrossRef
Pubmed
Google scholar
|
[56] |
Jindal R, Nahmias Y, Tilles A W, Berthiaume F, Yarmush M L. Amino acid-mediated heterotypic interaction governs performance of a hepatic tissue model. FASEB J, 2009, 23(7): 2288-2298
CrossRef
Pubmed
Google scholar
|
[57] |
Xiong A, Austin T W, Lagasse E, Uchida N, Tamaki S, Bordier B B, Weissman I L, Glenn J S, Millan M T. Isolation of human fetal liver progenitors and their enhanced proliferation by three-dimensional coculture with endothelial cells. Tissue Eng Part A, 2008, 14(6): 995-1006
CrossRef
Pubmed
Google scholar
|
[58] |
Hoshiba T, Cho C S, Murakawa A, Okahata Y, Akaike T. The effect of natural extracellular matrix deposited on synthetic polymers on cultured primary hepatocytes. Biomaterials, 2006, 27(26): 4519-4528
CrossRef
Pubmed
Google scholar
|
[59] |
Hoshiba T, Wakejima M, Cho C S, Shiota G, Akaike T. Different regulation of hepatocyte behaviors between natural extracellular matrices and synthetic extracellular matrices by hepatocyte growth factor. J Biomed Mater Res A, 2008, 85(1): 228-235
CrossRef
Pubmed
Google scholar
|
[60] |
Hidaka M, Su G N, Chen J K, Mukaisho K, Hattori T, Yamamoto G. Transplantation of engineered bone tissue using a rotary three-dimensional culture system. In Vitro Cell Dev Biol Anim, 2007, 43(2): 49-58
CrossRef
Pubmed
Google scholar
|
[61] |
Chen Z, Qi L Z, Zeng R, Li H Y, Dai L J. Stem cells and hepatic cirrhosis. Panminerva Med, 2010, 52(2): 149-165
Pubmed
|
[62] |
Russo F P, Alison M R, Bigger B W, Amofah E, Florou A, Amin F, Bou-Gharios G, Jeffery R, Iredale J P, Forbes S J. The bone marrow functionally contributes to liver fibrosis. Gastroenterology, 2006, 130(6): 1807-1821
CrossRef
Pubmed
Google scholar
|
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〈 | 〉 |