Received date: 02 Dec 2010
Accepted date: 23 Dec 2010
Published date: 05 Mar 2011
Copyright
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.
Key words： stem cell; liver disease; regenerative medicine
Jinzheng LI , Min LI , Bolin NIU , Jianping GONG . Therapeutic potential of stem cell in liver regeneration[J]. Frontiers of Medicine, 2011 , 5(1) : 26 -32 . DOI: 10.1007/s11684-011-0107-0
| 1 |
O’Leary J G, Lepe R, Davis G L. Indications for liver transplantation. Gastroenterology, 2008, 134(6): 1764-1776
|
| 2 |
Kung J W, Forbes S J. Stem cells and liver repair. Curr Opin Biotechnol, 2009, 20(5): 568-574
|
| 3 |
Ogawa S, Miyagawa S. Potentials of regenerative medicine for liver disease. Surg Today, 2009, 39(12): 1019-1025
|
| 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
|
| 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
|
| 6 |
Fausto N, Campbell J S, Riehle K J. Liver regeneration. Hepatology, 2006, 43 (Suppl 1): S45-S53
|
| 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
|
| 8 |
Dorrell C, Grompe M. Liver repair by intra- and extrahepatic progenitors. Stem Cell Rev, 2005, 1(1): 61-64
|
| 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
|
| 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
|
| 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
|
| 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
|
| 13 |
Sangan C B, Tosh D. Hepatic progenitor cells. Cell Tissue Res, 2010, 342(2): 131-137
|
| 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
|
| 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
|
| 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
|
| 17 |
Kallis Y N, Alison M R, Forbes S J. Bone marrow stem cells and liver disease. Gut, 2007, 56(5): 716-724
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 26 |
Liu Z J, Zhuge Y, Velazquez O C. Trafficking and differentiation of mesenchymal stem cells. J Cell Biochem, 2009, 106(6): 984-991
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 33 |
Dan Y Y, Yeoh G C. Liver stem cells: a scientific and clinical perspective. J Gastroenterol Hepatol, 2008, 23(5): 687-698
|
| 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
|
| 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
|
| 36 |
Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature, 2007, 448(7151): 313-317
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 50 |
Rodić N, Rutenberg M S, Terada N. Cell fusion and reprogramming: resolving our transdifferences. Trends Mol Med, 2004, 10(3): 93-96
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
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|
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