Abstract
Orthotopic liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a donor shortage. Liver tissue engineering may offer a promising strategy to solve this problem by providing transplantable, bioartificial livers. Diverse types of cells, biomaterials, and growth factor delivery systems have been tested for efficient regeneration of liver tissues that possess hepatic functions comparable to native livers. This article reviews recent advances in liver tissue engineering and describes cell sources, biomaterial scaffolds, and growth factor delivery systems that are currently being used to improve the regenerative potential of tissue-engineered livers.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Lundquist, F., N. Tygstrup, K. Winkler, K. Mellemgaard, and S. Munck-Petersen (1962) Ethanol metabolism and production of free acetate in the human liver. J. Clin. Invest. 41: 955–961.
Lobley, G. E., A. Connell, M. A. Lomax, D. S. Brown, E. Milne, A. G. Calder, and D. A. Farningham (1995) Hepatic detoxification of ammonia in the ovine liver: Possible consequences for amino acid catabolism. Br. J. Nutr. 73: 667–685.
Moshage, H. J., J. A. Janssen, J. H. Franssen, J. C. Hafkenscheid, and S. H. Yap (1987) Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. J. Clin. Invest. 79: 1635–1641.
Schwander, J. C., C. Hauri, J. Zapf, and E. R. Froesch (1983) Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: Dependence on growth hormone status. Endocrinol. 113: 297–305.
Michalopoulos, G. K. (2010) Liver regeneration after partial hepatectomy: Critical analysis of mechanistic dilemmas. Am. J. Pathol. 176: 2–13.
Kisseleva, T., E. Gigante, and D. A. Brenner (2010) Recent advances in liver stem cell therapy. Curr. Opin. Gastroenterol. 26: 395–402.
Zhang, W., L. Tucker-Kellogg, B. C. Narmada, L. Venkatraman, S. Chang, Y. Lu, N. Tan, J. K. White, R. Jia, S. S. Bhowmick, S. Shen, C. F. Dewey. Jr., and H. Yu (2010) Cell-delivery therapeutics for liver regeneration. Adv. Drug Deliv. Rev. 62: 814–826.
Mito, M., M. Kusano, and Y. Kawaura (1992) Hepatocyte transplantation in man. Transplant. Proc. 24: 3052–3053.
Habibullah, C. M., I. H. Syed, A. Qamar, and Z. Taher-Uz (1994) Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation 58: 951–952.
Strom, S. C., R. A. Fisher, M. T. Thompson, A. J. Sanyal, P. E. Cole, J. M. Ham, and M. P. Posner (1997) Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 63: 559–569.
Kobayashi, N., H. Noguchi, T. Watanabe, T. Matsumura, T. Totsugawa, T. Fujiwara, K. Westerman, P. Leboulch, I. J. Fox, and N. Tanaka (2000) Establishment of a tightly regulated human cell line for the development of hepatocyte transplantation. Hum. Cell 13: 7–13.
Terry, C. and R. D. Hughes (2009) An optimised method for cryopreservation of human hepatocytes. Methods Mol. Biol. 481: 25–34.
Terry, C., R. R. Mitry, S. C. Lehec, P. Muiesan, M. Rela, N. D. Heaton, R. D. Hughes, and A. Dhawan (2005) The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue. Cell Transplant. 14: 585–594.
Sgroi, A., V. Serre-Beinier, P. Morel, and L. Bühler (2009) What clinical alternatives to whole liver transplantation? Current status of artificial devices and hepatocyte transplantation. Transplantation 87: 457–466.
Thomson, J. A., J. Itskovitz-Eldor, S. S. Shapiro, M. A. Waknitz, J. J. Swiergiel, V. S. Marshall, and J. M. Jones (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.
Cai, J., Y. Zhao, Y. Liu, F. Ye, Z. Song, H. Qin, S. Meng, Y. Chen, R. Zhou, X. Song, Y. Guo, M. Ding, and H. Deng (2007) Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatol. 45: 1229–1239.
Basma, H., A. Soto-Gutiérrez, G. R. Yannam, L. Liu, R. Ito, T. Yamamoto, E. Ellis, S. D. Carson, S. Sato, Y. Chen, D Muirhead, N. Navarro-Álvarez, R. J. Wong, J. Roy-Chowdhury, J. L. Platt, D. F. Mercer, J. D. Miller, S. C. Storm, N. Kobayashi, and I. J. Fox (2009) Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterol. 136: 990–999.
Takahashi, K., K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861–872.
Hanna, J. H., K. Saha, and R. Jaenisch (2010) Pluripotency and cellular reprogramming: Facts, hypotheses, unresolved issues. Cell 143: 508–525.
Si-Tayeb, K., F. K. Noto, M. Nagaoka, J. Li, M. A. Battle, C. Duris, P. E. North, S. Dalton, and S. A. Duncan (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatol. 51: 297–305.
Espejel, S., G. R. Roll, K. J. McLaughlin, A. Y. Lee, J. Y. Zhang, D. J. Laird, K. Okita, S. Yamanaka, and H. Willenbring (2010) Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J. Clin. Invest. 120: 3120–3126.
Liu, H., Y. Kim, S. Sharkis, L. Marchionni, and Y. Y. Jang (2011) In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci. Transl. Med. 3: 82ra39.
Pittenger, M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147.
Li, T. Z., S. H. Shin, H. H. Cho, J. H. Kim, and H. Suh (2008) Growth factor-free cultured rat bone marrow derived mesenchymal stem cells towards hepatic progenitor cell differentiation. Biotechnol. Bioproc. Eng. 13: 659–665.
Stock, P., S. Brückner, S. Ebensing, M. Hempel, M. M. Dollinger, and B. Christ (2010) The generation of hepatocytes from mesenchymal stem cells and engraftment into murine liver. Nat. Protoc. 5: 617–627.
Li, T. Z., J. H. Kim, H. H. Cho, H. S. Lee, K. S. Kim, S. W. Lee, and H. Suh (2010) Therapeutic potential of bone-marrow-derived mesenchymal stem cells differentiated with growth-factor-free coculture method in liver-injured rats. Tissue Eng. Part A 16: 2649–2659.
Aurich, I., L. P. Mueller, H. Aurich, J. Luetzkendorf, K. Tisljar, M. M. Dollinger, W. Schormann, J. Walldorf, J. G. Hengstler, W. E. Fleig, and B. Christ (2007) Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut. 56: 405–415.
Aurich, H., M. Sgodda, P. Kaltwasser, M. Vetter, A. Weise, T. Liehr, M. Brulport, J. G. Hengstler, M. M. Dollinger, W. E. Fleig, and B. Christ (2009) Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut. 58: 570–581.
Pi, L., S. H. Oh, T. Shupe, and B. E. Petersen (2005) Role of connective tissue growth factor in oval cell response during liver regeneration after 2-AAF/PHx in rats. Gastroenterol. 128: 2077–2088.
Lemire, J. M., N. Shiojiri, and N. Fausto (1991) Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am. J. Pathol. 139: 535–552.
Wang, X., M. Foster, M. Al-Dhalimy, E. Lagasse, M. Finegold, and M. Grompe (2003) The origin and liver repopulating capacity of murine oval cells. Proc. Natl. Acad. Sci. USA 100Suppl 1: 11881–11888.
Yovchev, M. I., P. N. Grozdanov, H. Zhou, H. Racheria, C. Guha, and M. D. Dabeva (2008) Identification of adult hepatic progenitor cells capable of repopulating injured rat liver. Hepatol. 47: 636–647.
Khan, A. A., M. V. Shaik, N. Parveen, A. Rajendraprasad, M. A. Aleem, M. A Habeeb, G. Srinivas, T. A. Raj, S. K. Tiwari, K. Kumaresan, J. Venkateswarlu, G. Pande, and C. M. Habibullah (2010) Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant. 19: 409–418.
Oertel, M., A. Menthena, Y. Q. Chen, B. Teisner, C. H. Jensen, and D. A. Shafritz (2008) Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver. Gastroenterol. 134: 823–832.
Sandhu, J. S., P. M. Petkov, M. D. Dabeva, and D. A. Shafritz (2001) Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am. J. Pathol. 159: 1323–1334.
Kim, B. S. and D. J. Mooney (1998) Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 16: 224–230.
Lee, N. K., H. J. Oh, C. M. Hong, H. Suh, and S. H. Hong (2009) Comparison of the synthetic biodegradable polymers, polylactide (PLA), and polylactic-co-glycolic acid (PLGA) as scaffolds for artificial cartilage. Biotechnol. Bioproc. Eng. 14: 180–186.
Cho, S. W., S. S. Kim, J. W. Rhie, H. M. Cho, C. Y. Choi, and B. S. Kim (2005) Engineering of volume-stable adipose tissues. Biomat. 26: 3577–3585.
Cho, S. W., O. Jeon, J. E. Lim, S. J. Gwak, S. S. Kim, C. Y. Choi, D. I. Kim, and B. S. Kim (2006) Preliminary experience with tissue engineering of a venous vascular patch by using bone marrow-derived cells and a hybrid biodegradable polymer scaffold. J. Vasc. Surg. 44: 1329–1340.
Cho, S. W., K. W. Song, J. W. Rhie, M. H. Park, C. Y. Choi, and B. S. Kim (2007) Engineered adipose tissue formation enhanced by basic fibroblast growth factor and a mechanically stable environment. Cell Transplant. 16: 421–434.
Hasirci, V., F. Berthiaume, S. P. Bondre, J. D. Gresser, D. J. Trantolo, M. Toner, and D. L. Wise (2001) Expression of liver-specific functions by rat hepatocytes seeded in treated poly(lacticco-glycolic) acid biodegradable foams. Tissue Eng. 7: 385–394.
Kim, S. S., H. Utsunomiya, J. A. Koski, B. M. Wu, M. J. Cima, J. Sohn, K. Mukai, L. G. Griffith, and J. P. Vacanti (1998) Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. Ann. Surg. 228: 8–13.
Huang, H., S. Hanada, N. Kojima, and Y. Sakai (2006) Enhanced functional maturation of fetal porcine hepatocytes in three-dimensional poly-L-lactic acid scaffolds: A culture condition suitable for engineered liver tissues in large-scale animal studies. Cell Transplant. 15: 799–809.
Liu, T., S. Zhang, X. Chen, G. Li, and Y. Wang (2010) Hepatic differentiation of mouse embryonic stem cells in three-dimensional polymer scaffolds. Tissue Eng. Part A 16: 1115–1122.
Kazemnejad, S., A. Allameh, M. Soleimani, A. Gharehbaghian, Y. Mohammadi, N. Amirizadeh, and M. Jazayery (2009) Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold. J. Gastroenterol. Hepatol. 24: 278–287.
Piryaei, A., M. R. Valojerdi, M. Shahsavani, and H. Baharvand (2011) 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. 7: 103–118.
Farzaneh, Z., B. Pournasr, M. Ebrahimi, N. Aghdami, and H. Baharvand (2010) Enhanced functions of human embryonic stem cell-derived hepatocyte-like cells on three-dimensional nanofibrillar surfaces. Stem Cell Rev. 6: 601–610.
Hashemi, S. M., M. Soleimani, S. S. Zargarian, V. Haddadi-Asi, N. Ahmadbeigi, S. Soudi, Y. Gheisari, A. Hajarizadeh, and Y. Mohammadi (2009) In vitro differentiation of human cord bloodderived unrestricted somatic stem cells into hepatocyte-like cells on poly(epsilon-caprolactone) nanofiber scaffolds. Cells Tissues Organs 190: 135–149.
Tibbitt, M. W. and K. S. Anseth (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103: 655–663.
Lee, K. Y. and D. J. Mooney (2001) Hydrogels for tissue engineering. Chem. Rev. 101: 1869–1879.
Dvir-Ginzberg, M., I. Gamlieli-Bonshtein, R. Agbaria, and S. Cohen (2003) Liver tissue engineering within alginate scaffolds: Effects of cell-seeding density on hepatocyte viability, morphology, and function. Tissue Eng. 9: 757–766.
Dvir-Ginzberg, M., T. Elkayam, and S. Cohen (2008) Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds. FASEB J. 22: 1440–1449.
Lin, N., J. Lin, L. Bo, P. Weidong, S. Chen, and R. Xu (2010) Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells in an alginate scaffold. Cell Prolif. 43: 427–434.
Seo, Y. K., J. K. Park, K. Y. Song, S. Y. Kwon, and H. S. Lee (2010) Wound healing effect of collagen-hyaluronic acid implanted in partially injured anterior cruciate ligament of dog. Biotechnol. Bioproc. Eng. 15: 552–558.
Frost, S. J., R. H. Raja, and P. H. Weigel (1990) Characterization of an intracellular hyaluronic acid binding site in isolated rat hepatocytes. Biochem. 29: 10425–10432.
Katsuda, T., T. Teratani, T. Ochiya, and Y. Sakai (2010) Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson’s disease model rat. J. Biochem. 148: 281–288.
Zavan, B., P. Brun, V. Vindigni, A. Amadori, W. Habeler, P. Pontisso, D. Montemurro, G. Abatangelo, and R. Cortivo (2005) Extracellular matrix-enriched polymeric scaffolds as a substrate for hepatocyte cultures: In vitro and in vivo studies. Biomat. 26: 7038–7045.
Li, J., J. Pan, L. Zhang, and Y. Yu (2003) Culture of hepatocytes on fructose-modified chitosan scaffolds. Biomat. 24: 2317–2322.
Feng, Z. Q., X. Chu, N. P. Huang, T. Wang, Y. Wang, X. Shi, Y. Ding, and Z. Z. Gu (2009) The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver function. Biomat. 30: 2753–2763.
Schmidt, C. E. and J. M. Baier (2000) Acellular vascular tissues: Natural biomaterials for tissue repair and tissue engineering. Biomat. 21: 2215–2231.
Tamura, N., T. Nakamura, H. Terai, A. Iwakura, S. Nomura, Y. Shimizu, and M. Komeda (2003) A new acellular vascular prosthesis as a scaffold for host tissue regeneration. Int. J. Artif. Organs 26: 783–792.
Hawkins, J. A., N. D. Hillman, L. M. Lambert, J. Jones, G. B. Di Russo, T. Profaizer, T. C. Fuller, L. L. Minich, R. V. Williams, and R. E. Shaddy (2003) Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: Comparison with standard cryopreserved allografts. J. Thorac. Cardiovasc. Surg. 126: 247–252.
Ott, H. C., T. S. Matthiesen, S. K. Goh, L. D. Black, S. M. Kren, T. I. Netoff, and D. A. Taylor (2008) Perfusion-decellularized matrix: Using nature’s platform to engineer a bioartificial heart. Nat. Med. 14: 213–221.
Yoo, J. J., J. Meng, F. Oberpenning, and A. Atala (1998) Bladder augmentation using allogenic bladder submucosa seeded with cells. Urol. 51: 221–225.
Cho, S. W., S. H. Lim, I. K. Kim, Y. S. Hong, S. S. Kim, K. J. Yoo, H. Y. Park, Y. Jang, B. C. Chang, C. Y. Choi, K. C. Hwang, and B. S. Kim (2005) Small-diameter blood vessels engineered with bone marrow-derived cells. Ann. Surg. 241: 506–515.
Cho, S. W., J. E. Lim, H. S. Chu, H. J. Hyun, C. Y. Choi, K. C. Hwang, K. J. Yoo, D. I. Kim, and B. S. Kim (2006) Enhancement of in vivo endothelialization of tissue-engineered vascular grafts by granulocyte colony-stimulating factor. J. Biomed. Mater. Res. A 76: 252–263.
Cho, S.W., I. K. Kim, J. M. Kang, K. W. Song, H. S. Kim, C. H. Park, K. J. Yoo, and B. S. Kim (2009) Evidence for in vivo growth potential and vascular remodeling of tissue-engineered artery. Tissue Eng. Part A 15: 901–912.
Zheng, X. F., S. B. Lu, W. G. Zhang, S. Y. Liu, J. X. Huang, and Q. Y. Guo (2011) Mesenchymal stem cells on a decellularized cartilage matrix for cartilage tissue engineering. Biotechnol. Bioproc. Eng. 16: 593–602.
Macchiarini, P., P. Jungebluth, T. Go, M. A. Asnaghi, L. E. Rees, T. A. Cogan, A. Dodson, J. Martorell, S. Bellini, P. P. Parnigotto, S. C. Dickinson, A. P. Hollander, S. Mantero, M. T. Conconi, and M. A. Birchall (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372: 2023–2030.
Uygun, B. E., A. Soto-Gutierrez, H. Yagi, M. L. Izamis, M. A. Guzzardi, C. Shulman, J. Milwid, N. Kobayashi, A. Tilles, F. Berthiaume, M. Hertl, Y. Nahmias, M. L. Yarmush, and K. Uygun (2010) Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat. Med. 16: 814–820.
Baptista, P. M., M. M. Siddiqui, G. Lozier, S. R. Rodriguez, A. Atala, and S. Soker (2011) The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatol. 53: 604–617.
Soto-Gutierrez, A., L. Zhang, C. Medberry, K. Fukumitsu, D. Faulk, H. Jiang, J. Reing, R. Gramignoli, J. Komori, M. Ross, M. Nagaya, E. Lagasse, D. Stolz, S. C. Storm, I. J. Fox, and S. F. Badylak (2011) A whole-organ regenerative medicine approach for liver replacement. Tissue Eng. Part C Methods 17: 677–686.
Lang, R., M. M. Stern, L. Smith, Y. Liu, S. Bharadwaj, G. Liu, P. M. Baptista, C. R. Bergman, S. Soker, J. J. Yoo, A. Atala, and Y. Zhang (2011) Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. Biomat. 32: 7042–7052.
Wang, Y., C. B. Cui, M. Yamauchi, P. Miguez, M. Roach, R. Malavarca, M. J. Costello, V. Cardinale, E. Wauthier, C. Barbier, D. A. Gerber, D. Alvaro, and L. M. Reid (2011) Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatol. 53: 293–305.
Underhill, G. H., A. A. Chen, D. R. Albrecht, and S. N. Bhatia (2007) Assessment of hepatocellular function within PEG hydrogels. Biomat. 28: 256–270.
Itle, L. J., W. G. Koh, and M. V. Pishko (2005) Hepatocyte viability and protein expression within hydrogel microstructures. Biotechnol. Prog. 21: 926–932.
Chen, A. A., D. K. Thomas, L. L. Ong, R. E. Schwartz, T. R. Golub, and S. N. Bhatia (2011) Humanized mice with ectopic artificial liver tissues. Proc. Natl. Acad. Sci. USA 108: 11842–11847.
Wang, S., D. Nagrath, P. C. Chen, F. Berthiaume, and M. L. Yarmush (2008) Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide hydrogel. Tissue Eng. Part A 14: 227–236.
Genové, E., S. Schmitmeier, A. Sala, S. Borrós, A. Bader, L. G. Griffith, and C. E. Semino (2009) Functionalized self-assembling peptide hydrogel enhance maintenance of hepatocyte activity in vitro. J. Cell. Mol. Med. 13: 3387–3397.
Kedem, A., A. Perets, I. Gamlieli-Bonshtein, M. Dvir-Ginzberg, S. Mizrahi, and S. Cohen (2005) Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng. 11: 715–722.
Jeon, O., S. H. Ryu, J. H. Chung, and B. S. Kim (2005) Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin. J. Control. Release 105: 249–259.
Jeon, O., S. W. Kang, H. W. Lim, J. H. Chung, and B. S. Kim (2006) Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel. Biomat. 27: 1598–1607.
Cho, S. W., S. J. Gwak, S. W. Kang, S. H. Bhang, K. W. Song, Y. S. Yang, C. Y. Choi, and B. S. Kim (2006) Enhancement of angiogenic efficacy of human cord blood cell transplantation. Tissue Eng. 12: 1651–1661.
Bhang, S. H., S. W. Cho, J. M. Lim, J. M. Kang, T. J. Lee, H. S. Yang, Y. S. Song, M. H. Park, H. S. Kim, K. J. Yoo, Y. Jang, R. Langer, D. G. Anderson, and B. S. Kim (2009) Locally delivered growth factor enhances the angiogenic efficacy of adiposederived stromal cells transplanted to ischemic limbs. Stem Cells 27: 1976–1986.
Cho, S. W., I. K. Kim, S. H. Bhang, B. Joung, Y. J. Kim, K. J. Yoo, Y. S. Yang, C. Y. Choi, and B. S. Kim (2007) Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction. Eur. J. Heart Fail. 9: 974–985.
Hou, Y. T., H. Ljima, T. Takei, and K. Kawakami (2011) Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis. J. Biosci. Bioeng. 112: 265–272.
Lee, H., R. A. Cusick, F. Browne, T. Ho Kim, P. X. Ma, H. Utsunomiya, R. Langer, and J. P. Vacanti (2002) Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices. Transplantation 73: 1589–1593.
Hou, Y. T., H. Ljima, S. Matsumoto, T. Kubo, T. Takei, S. Sakai, and K. Kawakami (2010) Effect of a hepatocyte growth factor/heparin-immobilized collagen system on albumin synthesis and spheroid formation by hepatocytes. J. Biosci. Bioeng. 110: 208–216.
Kim, M., J. Y. Lee, C. N. Jones, A. Revzin, and G. Tae (2010) Heparin-based hydrogel as a matrix for encapsulation and cultivation of primary hepatocytes. Biomat. 31: 3596–3603.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, J.S., Cho, SW. Liver tissue engineering: Recent advances in the development of a bio-artificial liver. Biotechnol Bioproc E 17, 427–438 (2012). https://doi.org/10.1007/s12257-012-0047-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12257-012-0047-9