Skip to main content
SpringerLink
Log in

Treatment of Hepatic Malignances and Disorders: The Role of Liver Bioengineering

  • Chapter
  • First Online:
Advances in Stem Cell Therapy

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 1381 Accesses

Abstract

The liver, which is the largest gland in the body, performs hundreds of vital functions. Most of them are carried out by the hepatocytes that constitute about 80% of the liver’s total cell population. Despite being the main organ for numerous vital functions, the liver is the best example of an organ that possesses regenerative capacity following partial hepatectomy or toxic injury. During the regeneration process, the adaptive response and robustness of liver is crucial to ensure the body’s metabolic functions, and thus, if the liver has a disease, it may have a profound negative impact on metabolism and homeostasis of the body. Hence, we describe some of the most common liver diseases and novel regenerative therapies in development or already translated into the clinic that rely on liver regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. CDC. Center for Disease Control and Prevention. 2010. http://www.cdc.gov/nchs/fastats/liverdis.htm

  2. CDC. 2010. http://www.cdc.gov/injury/wisqars/pdf/10LCID_All_Deaths_By_Age_Group_2010-a.pdf

  3. Government Census. 2010. http://www.census.gov/prod/2010pubs/p25-1138.pdf

  4. Brill S, Zvibel I, Halpern Z, Oren R. The role of fetal and adult hepatocyte extracellular matrix in the regulation of tissue-specific gene expression in fetal and adult hepatocytes. Eur J Cell Biol. 2002;81(1):43–50.

    Article  CAS  PubMed  Google Scholar 

  5. Chelli D, Dimassi K, Salem A, Driss M, Zaanouni E, Zouaoui B, et al. Surgical treatment of breast lesions: preliminary results of the screening program of the Ariana area. Tunis Med. 2009;87(7):475–9.

    CAS  PubMed  Google Scholar 

  6. Greten TF, Manns MP, Reinisch I, Kaatsch P. Hepatocellular carcinoma occurring after successful treatment of childhood cancer with high dose chemotherapy and radiation. Gut. 2005;54(5):732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist. 2010;15 Suppl 4:14–22.

    Article  PubMed  Google Scholar 

  8. Zakim D, Boyer TD. Hepatology: a textbook of liver disease. 4th ed. Philadelphia: Saunders; 2003.

    Google Scholar 

  9. Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010;15 Suppl 4:5–13.

    Article  PubMed  Google Scholar 

  10. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.

    Article  CAS  PubMed  Google Scholar 

  11. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371(9615):838–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009;373(9682):2223–33.

    Article  PubMed  Google Scholar 

  13. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141(5):1572–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol. 2010;105(1):14–32; quiz 3.

    Article  PubMed  Google Scholar 

  15. Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002;36(5 Suppl 1):S30–4.

    Article  PubMed  Google Scholar 

  16. Bird GL, Williams R. Factors determining cirrhosis in alcoholic liver disease. Mol Aspects Med. 1988;10(2):97–105.

    Article  CAS  PubMed  Google Scholar 

  17. Bayard M, Holt J, Boroughs E. Nonalcoholic fatty liver disease. Am Fam Physician. 2006;73(11):1961–8.

    PubMed  Google Scholar 

  18. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346(16):1221–31.

    Article  CAS  PubMed  Google Scholar 

  19. Nguyen TA, Sanyal AJ. Pathophysiology guided treatment of nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2012;27 Suppl 2:58–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ibrahim SH, Kohli R, Gores GJ. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. 2011;53(2):131–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011;332(6037):1519–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Masuoka HC, Chalasani N. Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann N Y Acad Sci. 2013;1281:106–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee WM. Acute liver failure. Semin Respir Crit Care Med. 2012;33(1):36–45.

    Article  PubMed  Google Scholar 

  24. Lee W, Williams R, editors. Acute liver failure. 1st ed. Cambridge: Cambridge University Press; 1997.

    Google Scholar 

  25. Lee WM. Acute liver failure. N Engl J Med. 1993;329(25):1862–72.

    Article  CAS  PubMed  Google Scholar 

  26. CDC. Center for Disease Control. http://www.cdc.gov/hepatitis/

  27. Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003;362(9401):2089–94.

    Article  CAS  PubMed  Google Scholar 

  28. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003;362(9401):2095–100.

    Article  CAS  PubMed  Google Scholar 

  29. Hansen K, Horslen S. Metabolic liver disease in children. Liver Transpl. 2008;14(5):713–33.

    Article  PubMed  Google Scholar 

  30. Mazariegos G, Shneider B, Burton B, Fox IJ, Hadzic N, Kishnani P, et al. Liver transplantation for pediatric metabolic disease. Mol Genet Metab. 2014;111(4):418–27.

    Article  CAS  PubMed  Google Scholar 

  31. Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991;324(26):1852–7.

    Article  CAS  PubMed  Google Scholar 

  32. Evangelopoulos ME, Evangelopoulos DS, Potagas C, Sfagos C. Homonymous hemianopsia as the leading symptom of a tumor like demyelinating lesion: a case report. Cases J. 2009;2:9366.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Organ Procurement and Transplantation Network: National Data. 2011. http://optn.transplant.hrsa.gov/. Accessed 1 Nov 2011.

  34. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2011;53(2):604–17.

    Article  CAS  PubMed  Google Scholar 

  35. Pomfret EA, Fryer JP, Sima CS, Lake JR, Merion RM. Liver and intestine transplantation in the United States, 1996-2005. Am J Transplant. 2007;7(5):1376–89.

    Article  CAS  PubMed  Google Scholar 

  36. D’Alessandro AM, Hoffmann RM, Knechtle SJ, Odorico JS, Becker YT, Musat A, et al. Liver transplantation from controlled non-heart-beating donors. Surgery. 2000;128(4):579–86.

    Article  PubMed  Google Scholar 

  37. Reich DJ, Munoz SJ, Rothstein KD, Nathan HM, Edwards JM, Hasz RD, et al. Controlled non-heart-beating donor liver transplantation—a successful single center experience, with topic update. Transplantation. 2000;70(8):1159–66.

    Article  CAS  PubMed  Google Scholar 

  38. Testa G, Goldstein RM, Netto G, Abbasoglu O, Brooks BK, Levy MF, et al. Long-term outcome of patients transplanted with livers from hepatitis C-positive donors. Transplantation. 1998;65(7):925–9.

    Article  CAS  PubMed  Google Scholar 

  39. Vargas HE, Laskus T, Wang LF, Lee R, Radkowski M, Dodson F, et al. Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology. 1999;117(1):149–53.

    Article  CAS  PubMed  Google Scholar 

  40. Loggi E, Micco L, Ercolani G, Cucchetti A, Bihl FK, Grazi GL, et al. Liver transplantation from hepatitis B surface antigen positive donors: a safe way to expand the donor pool. J Hepatol. 2012;56(3):579–85.

    Article  PubMed  Google Scholar 

  41. Emond JC, Freeman RB, Renz JF, Yersiz H, Rogiers X, Busuttil RW. Optimizing the use of donated cadaver livers: analysis and policy development to increase the application of split-liver transplantation. Liver Transpl. 2002;8(10):863–72.

    Article  PubMed  Google Scholar 

  42. Vagefi PA, Parekh J, Ascher NL, Roberts JP, Freise CE. Outcomes with split liver transplantation in 106 recipients: the University of California, San Francisco, experience from 1993 to 2010. Arch Surg. 2011;146(9):1052–9.

    Article  PubMed  Google Scholar 

  43. Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, et al. Successful ex-vivo gene-therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genet. 1994;6(4):335–41.

    Article  CAS  PubMed  Google Scholar 

  44. Grossman M, Rader DJ, Muller DWM, Kolansky DM, Kozarsky K, Clark BJ, et al. A pilot-study of ex-vivo gene-therapy for homozygous familial hypercholesterolemia. Nat Med. 1995;1(11):1148–54.

    Article  CAS  PubMed  Google Scholar 

  45. Fisher RA, Strom SC. Human hepatocyte transplantation: worldwide results. Transplantation. 2006;82(4):441–9.

    Article  PubMed  Google Scholar 

  46. Strom SC, Chowdhury JR, Fox IJ. Hepatocyte transplantation for the treatment of human disease. Semin Liver Dis. 1999;19(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  47. Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998;338(20):1422–6.

    Article  CAS  PubMed  Google Scholar 

  48. Hughes RD, Mitry RR, Dhawan A. Hepatocyte transplantation for metabolic liver disease: UK experience. J R Soc Med. 2005;98(8):341–5.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ambrosino G, Varotto S, Strom SC, Guariso G, Franchin E, Miotto D, et al. Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 2005;14(2–3):151–7.

    Article  PubMed  Google Scholar 

  50. Dhawan A, Mitry RR, Hughes RD, Lehec S, Terry C, Bansal S, et al. Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. 2004;78(12):1812–4.

    Article  PubMed  Google Scholar 

  51. Muraca M, Gerunda G, Neri D, Vilei MT, Granato A, Feltracco P, et al. Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet. 2002;359(9303):317–8.

    Article  PubMed  Google Scholar 

  52. Sokal EM, Smets F, Bourgois A, Van Maldergem L, Buts JP, Reding R, et al. Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up. Transplantation. 2003;76(4):735–8.

    Article  PubMed  Google Scholar 

  53. Strom SC, Fisher RA, Rubinstein WS, Barranger JA, Towbin RB, Charron M, et al. Transplantation of human hepatocytes. Transplant Proc. 1997;29(4):2103–6.

    Article  CAS  PubMed  Google Scholar 

  54. Horslen SP, McCowan TC, Goertzen TC, Warkentin PI, Cai HB, Strom SC, et al. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics. 2003;111(6 Pt 1):1262–7.

    Article  PubMed  Google Scholar 

  55. Mitry RR, Dhawan A, Hughes RD, Bansal S, Lehec S, Terry C, et al. One liver, three recipients: segment IV from split-liver procedures as a source of hepatocytes for cell transplantation. Transplantation. 2004;77(10):1614–6.

    Article  PubMed  Google Scholar 

  56. Strom SC, Fisher RA, Thompson MT, Sanyal AJ, Cole PE, Ham JM, et al. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation. 1997;63(4):559–69.

    Article  CAS  PubMed  Google Scholar 

  57. Soltys KA, Soto-Gutierrez A, Nagaya M, Baskin KM, Deutsch M, Ito R, et al. Barriers to the successful treatment of liver disease by hepatocyte transplantation. J Hepatol. 2010;53(4):769–74.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Mito M, Kusano M, Kawaura Y. Hepatocyte transplantation in man. Transplant Proc. 1992;24(6):3052–3.

    CAS  PubMed  Google Scholar 

  59. Fox IJ, Chowdhury NR, Gupta S, Kondapalli R, Schilsky ML, Stockert RJ, et al. Conditional immortalization of Gunn rat hepatocytes—an ex-vivo model for evaluating methods for bilirubin-UDP-glucuronosyltransferase gene-transfer. Hepatology. 1995;21(3):837–46.

    CAS  PubMed  Google Scholar 

  60. Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Habeeb MA, et al. Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant. 2010;19(4):409–18.

    PubMed  Google Scholar 

  61. Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao H-L, et al. Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 2007;204(8):1973–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Basma H, Soto-Gutierrez A, Yannam GR, Liu L, Ito R, Yamamoto T, et al. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology. 2009;136(3):990–9.

    Article  CAS  PubMed  Google Scholar 

  63. Liu H, Kim Y, Sharkis S, Marchionni L, Jang Y-Y. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci Transl Med. 2011;3(82):82ra39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Kharaziha P, Hellstrom PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, et al. 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(10):1199–205.

    Article  CAS  PubMed  Google Scholar 

  65. Salama H, Zekri A-R, Zern M, Bahnassy A, Loutfy S, Shalaby S, et al. Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transplant. 2010;19(11):1475–86.

    Article  PubMed  Google Scholar 

  66. Pai M, Zacharoulis D, Milicevic MN, Helmy S, Jiao LR, Levicar N, et al. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol. 2008;103(8):1952–8.

    Article  CAS  PubMed  Google Scholar 

  67. Gouon-Evans V, Boussemart L, Gadue P, Nierhoff D, Koehler CI, Kubo A, et al. BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nat Biotechnol. 2006;24(11):1402–11.

    Article  CAS  PubMed  Google Scholar 

  68. Gadue P, Huber TL, Paddison PJ, Keller GM. Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells. Proc Natl Acad Sci U S A. 2006;103(45):16806–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Combs C, Brunt EM, Solomon H, Bacon BR, Brantly M, Di Bisceglie AM. Rapid development of hepatic alpha1-antitrypsin globules after liver transplantation for chronic hepatitis C. Gastroenterology. 1997;112(4):1372–5.

    Article  CAS  PubMed  Google Scholar 

  70. Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, et al. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011;54(3):820–8.

    Article  PubMed  Google Scholar 

  71. Spahr L, Chalandon Y, Terraz S, Kindler V, Rubbia-Brandt L, Frossard JL, et al. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial. PLoS One. 2013;8(1):e53719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Guha C, Sharma A, Gupta S, Alfieri A, Gorla GR, Gagandeep S, et al. Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation. Cancer Res. 1999;59(23):5871–4.

    CAS  PubMed  Google Scholar 

  73. Guha C, Parashar B, Deb NJ, Garg M, Gorla GR, Singh A, et al. Normal hepatocytes correct serum bilirubin after repopulation of Gunn rat liver subjected to irradiation/partial resection. Hepatology. 2002;36(2):354–62.

    Article  PubMed  Google Scholar 

  74. Zhou HC, Dong XY, Kabarriti R, Chen Y, Avsar Y, Wang X, et al. Single liver lobe repopulation with wildtype hepatocytes using regional hepatic irradiation cures jaundice in Gunn rats. PLoS One. 2012;7(10):e46775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Laconi E, Oren R, Mukhopadhyay DK, Hurston E, Laconi S, Pani P, et al. Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol. 1998;153(1):319–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Landis CS, Yamanouchi K, Zhou HC, Mohan S, Roy-Chowdhury N, Shafritz DA, et al. Noninvasive evaluation of liver repopulation by transplanted hepatocytes using P-31 MRS imaging in mice. Hepatology. 2006;44(5):1250–8.

    Article  CAS  PubMed  Google Scholar 

  77. Verma IM, Weitzman MD. Gene therapy: twenty-first century medicine. Annu Rev Biochem. 2005;74:711–38.

    Article  CAS  PubMed  Google Scholar 

  78. Herskowitz I. Functional inactivation of genes by dominant negative mutations. Nature. 1987;329(6136):219–22.

    Article  CAS  PubMed  Google Scholar 

  79. Schmitz V, Qian C, Ruiz J, Sangro B, Melero I, Mazzolini G, et al. Gene therapy for liver diseases: recent strategies for treatment of viral hepatitis and liver malignancies. Gut. 2002;50(1):130–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gonzalez-Aseguinolaza G, Prieto J. Gene therapy of liver diseases: a 2011 perspective. Clin Res Hepatol Gastroenterol. 2011;35(11):699–708.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang WW. Development and application of adenoviral vectors for gene therapy of cancer. Cancer Gene Ther. 1999;6(2):113–38.

    Article  CAS  PubMed  Google Scholar 

  82. Qian C, Drozdzik M, Caselmann WH, Prieto J. The potential of gene therapy in the treatment of hepatocellular carcinoma. J Hepatol. 2000;32(2):344–51.

    Article  CAS  PubMed  Google Scholar 

  83. Patijn GA, Kay MA. Hepatic gene therapy using adeno-associated virus vectors. Semin Liver Dis. 1999;19(1):61–9.

    Article  CAS  PubMed  Google Scholar 

  84. Snyder RO, Miao CH, Patijn GA, Spratt SK, Danos O, Nagy D, et al. Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat Genet. 1997;16(3):270–6.

    Article  CAS  PubMed  Google Scholar 

  85. Flotte TR, Mueller C. Gene therapy for alpha-1 antitrypsin deficiency. Hum Mol Genet. 2011;20:R87–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Paulk NK, Wursthorn K, Wang Z, Finegold MJ, Kay MA, Grompe M. Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo. Hepatology. 2010;51(4):1200–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sands MS, Davidson BL. Gene therapy for lysosomal storage diseases. Mol Ther. 2006;13(5):839–49.

    Article  CAS  PubMed  Google Scholar 

  88. Ziegler RJ, Yew NS, Li C, Cherry M, Berthelette PC, Romanczuk H, et al. Correction of enzymatic and lysosomal storage defects in Fabry mice by adenovirus-mediated gene transfer. Hum Gene Ther. 1999;10(10):1667–82.

    Article  CAS  PubMed  Google Scholar 

  89. Du H, Heur M, Witte DP, Ameis D, Grabowski GA. Lysosomal acid lipase deficiency: correction of lipid storage by adenovirus-mediated gene transfer in mice. Hum Gene Ther. 2002;13(11):1361–72.

    Article  CAS  PubMed  Google Scholar 

  90. Li H, Zhang B, Lu Y, Jorgensen M, Petersen B, Song S. Adipose tissue-derived mesenchymal stem cell-based liver gene delivery. J Hepatol. 2011;54(5):930–8.

    Article  CAS  PubMed  Google Scholar 

  91. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.

    Article  CAS  PubMed  Google Scholar 

  92. Im SJ, Yang SH, Yoon SK, Sung YC. Increase of plasma IL-12/p40 ratio induced by the combined therapy of DNA vaccine and lamivudine correlates with sustained viremia control in CHB carriers. Immune Netw. 2009;9(1):20–6.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Arbuthnot P. Harnessing RNA, interference for the treatment of viral infections. Drug News Perspect. 2010;23(6):341–50.

    CAS  PubMed  Google Scholar 

  94. Ueki T, Kaneda Y, Tsutsui H, Naknishi K, Sawa Y, Morishita R, Matsumoto K, Nakamura T, Takahashi H, Okamoto E, Fujimoto J. Hepatocyte growth factor gen therapy of liver cirrhosis in rats. Nat Med. 1999;5(2):226–30.

    Article  CAS  PubMed  Google Scholar 

  95. Sobrevals L, Rodriguez C, Romero-Trevejo JL, Gondi G, Monreal I, Pañeda A, Juanarena N, Arcelus S, Razquin N, Guembe L, González-Asequinolaza G, Prieto J, Fortes P. Insuline like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrosis reversión in rats. Hepatology. 2010;51(3):912–21.

    CAS  PubMed  Google Scholar 

  96. Descamps D, Vigant F, Esselin S, Connault E, Opolon P, Perricaudet M, et al. Expression of non-signaling membrane-anchored death receptors protects murine livers in different models of hepatitis. Hepatology. 2006;44(2):399–409.

    Article  CAS  PubMed  Google Scholar 

  97. Grossfeld GD, Ginsberg DA, Stein JP, Bochner BH, Esrig D, Groshen S, et al. Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression. J Natl Cancer Inst. 1997;89(3):219–27.

    Article  CAS  PubMed  Google Scholar 

  98. Mercola D, Cohen JS. Antisense approaches to cancer gene therapy. Cancer Gene Ther. 1995;2(1):47–59.

    CAS  PubMed  Google Scholar 

  99. Uygun B, Soto-Gutierrez A, Yagi H, Izamis M, Guzzardi M, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16(7):814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–21.

    Article  CAS  PubMed  Google Scholar 

  101. Kim BS, Baez CE, Atala A. Biomaterials for tissue engineering. World J Urol. 2000;18(1):2–9.

    Article  CAS  PubMed  Google Scholar 

  102. Atala A, Kasper FK, Mikos AG. Engineering complex tissues. Sci Transl Med. 2012;4(160):160rv12.

    Article  PubMed  CAS  Google Scholar 

  103. Lin P, Chan WC, Badylak SF, Bhatia SN. Assessing porcine liver-derived biomatrix for hepatic tissue engineering. Tissue Eng. 2004;10(7–8):1046–53.

    Article  CAS  PubMed  Google Scholar 

  104. Yagi H, Fukumitsu K, Fukuda K, Kitago M, Shinoda M, Obara H, et al. Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach. Cell Transplant. 2013;22(2):231–42.

    Article  PubMed  Google Scholar 

  105. Carpentier B, Gautier A, Legallais C. Artificial and bioartificial liver devices: present and future. Gut. 2009;58(12):1690–702.

    Article  CAS  PubMed  Google Scholar 

  106. Phua J, Lee KH. Liver support devices. Curr Opin Crit Care. 2008;14(2):208–15.

    Article  PubMed  Google Scholar 

  107. Banares R, Catalina MV, Vaquero J. Liver support systems: will they ever reach prime time? Curr Gastroenterol Rep. 2013;15(3):312.

    Article  PubMed  Google Scholar 

  108. Pless G. Artificial and bioartificial liver support. Organogenesis. 2007;3(1):20–4.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Rifai K. Extracorporeal albumin dialysis. Hepatol Res. 2008;38 Suppl 1:S41–5.

    Article  PubMed  Google Scholar 

  110. Brophy CM, Nyberg SL. Extracorporeal treatment of acute liver failure. Hepatol Res. 2008;38 Suppl 1:S34–40.

    Article  PubMed  Google Scholar 

  111. Park JK, Lee DH. Bioartificial liver systems: current status and future perspective. J Biosci Bioeng. 2005;99(4):311–9.

    Article  CAS  PubMed  Google Scholar 

  112. Cao S, Esquivel CO, Keeffe EB. New approaches to supporting the failing liver. Annu Rev Med. 1998;49:85–94.

    Article  CAS  PubMed  Google Scholar 

  113. Stange J, Mitzner S. Cell sources for bioartificial liver support. Int J Artif Organs. 1996;19(1):14–7.

    CAS  PubMed  Google Scholar 

  114. Podoll AS, DeGolovine A, Finkel KW. Liver support systems—a review. ASAIO J. 2012;58(5):443–9.

    Article  CAS  PubMed  Google Scholar 

  115. Tilles AW, Berthiaume F, Yarmush ML, Tompkins RG, Toner M. Bioengineering of liver assist devices. J Hepatobiliary Pancreat Surg. 2002;9(6):686–96.

    Article  PubMed  Google Scholar 

  116. Yu CB, Pan XP, Li LJ. Progress in bioreactors of bioartificial livers. Hepatobiliary Pancreat Dis Int. 2009;8(2):134–40.

    PubMed  Google Scholar 

  117. Ellis AJ, Hughes RD, Wendon JA, Dunne J, Langley PG, Kelly JH, et al. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology. 1996;24(6):1446–51.

    Article  CAS  PubMed  Google Scholar 

  118. Demetriou AA, Brown Jr RS, Busuttil RW, Fair J, McGuire BM, Rosenthal P, et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg. 2004;239(5):660–7; discussion 7–70.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Patzer 2nd JF, Mazariegos GV, Lopez R, Molmenti E, Gerber D, Riddervold F, et al. Novel bioartificial liver support system: preclinical evaluation. Ann N Y Acad Sci. 1999;875:340–52.

    Article  PubMed  Google Scholar 

  120. Flendrig LM, la Soe JW, Jorning GG, Steenbeek A, Karlsen OT, Bovee WM, et al. In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates. J Hepatol. 1997;26(6):1379–92.

    Article  CAS  PubMed  Google Scholar 

  121. Sauer IM, Kardassis D, Zeillinger K, Pascher A, Gruenwald A, Pless G, et al. Clinical extracorporeal hybrid liver support—phase I study with primary porcine liver cells. Xenotransplantation. 2003;10(5):460–9.

    Article  CAS  PubMed  Google Scholar 

  122. McKenzie TJ, Lillegard JB, Nyberg SL. Artificial and bioartificial liver support. Semin Liver Dis. 2008;28(2):210–7.

    Article  PubMed  Google Scholar 

  123. Adham M. Extracorporeal liver support: waiting for the deciding vote. ASAIO J. 2003;49(6):621–32.

    Article  PubMed  Google Scholar 

  124. Barakat O, Abbasi S, Rodriguez G, Rios J, Wood RP, Ozaki C, et al. Use of decellularized porcine liver for engineering humanized liver organ. J Surg Res. 2012;173(1):e11–25.

    Article  CAS  PubMed  Google Scholar 

  125. Lang R, Stern MM, Smith L, Liu Y, Bharadwaj S, Liu G, et al. Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. Biomaterials. 2011;32(29):7042–52.

    Article  CAS  PubMed  Google Scholar 

  126. Shupe T, Williams M, Brown A, Willenberg B, Petersen BE. Method for the decellularization of intact rat liver. Organogenesis. 2010;6(2):134–6.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Liu Y, Yang B, Ma J, Wang H, Huang F, Zhang J, et al. Interleukin-21 maintains the expression of CD16 on monocytes via the production of IL-10 by human naive CD4+ T cells. Cell Immunol. 2011;267(2):102–8.

    Article  CAS  PubMed  Google Scholar 

  128. Pless G. Bioartificial liver support systems. Methods Mol Biol. 2010;640:511–23.

    Article  CAS  PubMed  Google Scholar 

  129. Watanabe FD, Mullon CJ, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi S, et al. Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Ann Surg. 1997;225(5):484–91; discussion 91–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Nibourg GA, Chamuleau RA, van der Hoeven TV, Maas MA, Ruiter AF, Lamers WH, et al. Liver progenitor cell line HepaRG differentiated in a bioartificial liver effectively supplies liver support to rats with acute liver failure. PLoS One. 2012;7(6):e38778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Zhao LF, Pan XP, Li LJ. Key challenges to the development of extracorporeal bioartificial liver support systems. Hepatobiliary Pancreat Dis Int. 2012;11(3):243–9.

    Article  PubMed  Google Scholar 

  132. Sgroi A, Mai G, Morel P, Baertschiger RM, Gonelle-Gispert C, Serre-Beinier V, et al. Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration. Cell Transplant. 2011;20(11–12):1791–803.

    Article  PubMed  Google Scholar 

  133. Umehara Y, Hakamada K, Seino K, Aoki K, Toyoki Y, Sasaki M. Improved survival and ammonia metabolism by intraperitoneal transplantation of microencapsulated hepatocytes in totally hepatectomized rats. Surgery. 2001;130(3):513–20.

    Article  CAS  PubMed  Google Scholar 

  134. Joly A, Desjardins JF, Fremond B, Desille M, Campion JP, Malledant Y, et al. Survival, proliferation, and functions of porcine hepatocytes encapsulated in coated alginate beads: a step toward a reliable bioartificial liver. Transplantation. 1997;63(6):795–803.

    Article  CAS  PubMed  Google Scholar 

  135. Honiger J, Balladur P, Mariani P, Calmus Y, Vaubourdolle M, Delelo R, et al. Permeability and biocompatibility of a new hydrogel used for encapsulation of hepatocytes. Biomaterials. 1995;16(10):753–9.

    Article  CAS  PubMed  Google Scholar 

  136. Miranda LE, Capellini VK, Reis GS, Celotto AC, Carlotti Jr CG, Evora PR. Effects of partial liver ischemia followed by global liver reperfusion on the remote tissue expression of nitric oxide synthase: lungs and kidneys. Transplant Proc. 2010;42(5):1557–62.

    Article  CAS  PubMed  Google Scholar 

  137. Shi XL, Zhang Y, Gu JY, Ding YT. Coencapsulation of hepatocytes with bone marrow mesenchymal stem cells improves hepatocyte-specific functions. Transplantation. 2009;88(10):1178–85.

    Article  PubMed  Google Scholar 

  138. Zhang FT, Wan HJ, Li MH, Ye J, Yin MJ, Huang CQ, et al. Transplantation of microencapsulated umbilical-cord-blood-derived hepatic-like cells for treatment of hepatic failure. World J Gastroenterol. 2011;17(7):938–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Kim M, Lee JY, Jones CN, Revzin A, Tae G. Heparin-based hydrogel as a matrix for encapsulation and cultivation of primary hepatocytes. Biomaterials. 2010;31(13):3596–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Bandi S, Joseph B, Berishvili E, Singhania R, Wu YM, Cheng K, et al. Perturbations in ataxia telangiectasia mutant signaling pathways after drug-induced acute liver failure and their reversal during rescue of animals by cell therapy. Am J Pathol. 2011;178(1):161–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Viswanathan P, Gupta S. New directions for cell-based therapies in acute liver failure. J Hepatol. 2012;57(4):913–5.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Cheng N, Wauthier E, Reid LM. Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated hepatoblasts. Tissue Eng Part A. 2008;14(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  143. Qiu L, Wang J, Wen X, Wang H, Wang Y, Lin Q, et al. Transplantation of co-microencapsulated hepatocytes and HUVECs for treatment of fulminant hepatic failure. Int J Artif Organs. 2012;35(6):458–65.

    Article  CAS  PubMed  Google Scholar 

  144. Komori J, Boone L, DeWard A, Hoppo T, Lagasse E. The mouse lymph node as an ectopic transplantation site for multiple tissues. Nat Biotechnol. 2012;30(10):976–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Hoppo T, Komori J, Manohar R, Stolz DB, Lagasse E. Rescue of lethal hepatic failure by hepatized lymph nodes in mice. Gastroenterology. 2011;140(2):656–66 e2.

    Article  CAS  PubMed  Google Scholar 

  146. Pediaditakis P, Monga SPS, Mars WM, Michalopoulos GK. Differential mitogenic effects of single chain hepatocyte growth factor (HGF)/scatter factor and HGF/NK1 following cleavage by factor Xa. J Biol Chem. 2002;277(16):14109–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Naldini L, Vigna E, Narsimhan RP, Gaudino G, Zarnegar R, Michalopoulos GK, et al. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991;6(4):501–4.

    CAS  PubMed  Google Scholar 

  148. Matsumoto K, Nakamura T. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun. 1997;239(3):639–44.

    Article  CAS  PubMed  Google Scholar 

  149. Ishikawa H, Jo JI, Tabata Y. Liver anti-fibrosis therapy with mesenchymal stem cells secreting hepatocyte growth factor. J Biomater Sci Polym Ed. 2011;23(18):2259–72.

    Google Scholar 

  150. Ichihara A. BCA, HGF, and proteasomes. Biochem Biophys Res Commun. 1999;266(3):647–51.

    Article  CAS  PubMed  Google Scholar 

  151. Sellaro TL, Ranade A, Faulk DM, McCabe GP, Dorko K, Badylak SF, et al. Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels. Tissue Eng Part A. 2010;16(3):1075–82.

    Article  CAS  PubMed  Google Scholar 

  152. Kwiecinski M, Noetel A, Elfimova N, Trebicka J, Schievenbusch S, Strack I, et al. Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells by miRNA-29 induction. PLoS One. 2011;6(9):e24568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Mullhaupt B, Feren A, Fodor E, Jones A. Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration. J Biol Chem. 1994;269(31):19667–70.

    CAS  PubMed  Google Scholar 

  154. Mullhaupt B, Feren A, Jones A, Fodor E. DNA sequence and functional characterization of the human and rat epidermal growth factor promoter: regulation by cell growth. Gene. 2000;250(1–2):191–200.

    Article  CAS  PubMed  Google Scholar 

  155. Casillas-Ramirez A, Zaouali A, Padrissa-Altes S, Ben Mosbah I, Pertosa A, Alfany-Fernandez I, et al. Insulin-like growth factor and epidermal growth factor treatment: new approaches to protecting steatotic livers against ischemia-reperfusion injury. Endocrinology. 2009;150(7):3153–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Ohlsson C, Mohan S, Sjogren K, Tivesten A, Isgaard J, Isaksson O, et al. The role of liver-derived insulin-like growth factor-I. Endocr Rev. 2009;30(5):494–535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Oe S, Fukunaka Y, Hirose T, Yamaoka Y, Tabata Y. A trial on regeneration therapy of rat liver cirrhosis by controlled release of hepatocyte growth factor. J Control Release. 2003;88(2):193–200.

    Article  CAS  PubMed  Google Scholar 

  158. Kedem A, Perets A, Gamlieli-Bonshtein I, Dvir-Ginzberg M, Mizrahi S, Cohen S. Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng. 2005;11(5–6):715–22.

    Article  CAS  PubMed  Google Scholar 

  159. Kmiec Z. Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol. 2001;161:III–XIII, 1–151.

    CAS  PubMed  Google Scholar 

  160. Skrtic S, Wallenius V, Ekberg S, Brenzel A, Gressner AM, Jansson JO. Hepatocyte-stimulated expression of hepatocyte growth factor (HGF) in cultured rat hepatic stellate cells. J Hepatol. 1999;30(1):115–24.

    Article  CAS  PubMed  Google Scholar 

  161. Tomiya T, Nishikawa T, Inoue Y, Ohtomo N, Ikeda H, Tejima K, et al. Leucine stimulates HGF production by hepatic stellate cells through mTOR pathway. Biochem Biophys Res Commun. 2007;358(1):176–80.

    Article  CAS  PubMed  Google Scholar 

  162. Xi J, Wang Y, Zhang P, He L, Nan X, Yue W, et al. Human fetal liver stromal cells that overexpress bFGF support growth and maintenance of human embryonic stem cells. PLoS One. 2010;5(12):e14457.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Teng Y, Wang Y, Li S, Wang W, Gu R, Guo X, et al. Treatment of acute hepatic failure in mice by transplantation of mixed microencapsulation of rat hepatocytes and transgenic human fetal liver stromal cells. Tissue Eng Part C Methods. 2010;16(5):1125–34.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Instituto de Investigación Sanitaria de Aragón (IIS), Avda San Juan Bosco, 13, Zaragoza, Aragón, 50.009, Spain

      Pilar Sainz-Arnal, Iris Plá-Palacín, Natalia Sánchez-Romero & Pedro M. Baptista Pharm.D., Ph.D.

    2. Aragon’s Health Science Institutes (IACS), Avda San Juan Bosco, 13, Zaragoza, Aragón, 50.009, Spain

      Pilar Sainz-Arnal & Natalia Sánchez-Romero

    3. CIBERehd, Zaragoza, Spain

      Pedro M. Baptista Pharm.D., Ph.D.

    Authors
    1. Pilar Sainz-Arnal
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Iris Plá-Palacín
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Natalia Sánchez-Romero
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Pedro M. Baptista Pharm.D., Ph.D.
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Pedro M. Baptista Pharm.D., Ph.D. .

    Editor information

    Editors and Affiliations

    1. Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Zayed City, Egypt

      Nagwa El-Badri

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2017 Springer International Publishing Switzerland

    About this chapter

    Cite this chapter

    Sainz-Arnal, P., Plá-Palacín, I., Sánchez-Romero, N., Baptista, P.M. (2017). Treatment of Hepatic Malignances and Disorders: The Role of Liver Bioengineering. In: El-Badri, N. (eds) Advances in Stem Cell Therapy. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-29149-9_12

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation