Skip to main content

Integration of Technologies for Hepatic Tissue Engineering

  • Chapter
  • First Online:
Tissue Engineering II

Abstract

The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25 000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen “sandwich” and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Zakim D, Boyer T (1996) Hepatology: A textbook of liver disease. W.B. Saunders, Philadelphia

    Google Scholar 

  2. Desmet VJ (2001) In: Arias IM (ed) The liver, biology and pathobiology. Lippincott Williams & Wilkins, Philadelphia, p 3

    Google Scholar 

  3. Taub R (2004) Nat Rev Mol Cell Biol 5:836

    Article  CAS  Google Scholar 

  4. Dahn MS, Lange MP, Berberoglu ED (1996) Shock 6:52

    Article  CAS  Google Scholar 

  5. Lee K, Berthiaume F, Stephanopoulos GN, Yarmush ML (2003) Biotechnol Bioeng 83:400

    Article  CAS  Google Scholar 

  6. Ramadori G, Christ B (1999) Semin Liver Dis 19:141

    Article  CAS  Google Scholar 

  7. Nedredal GI, Elvevold KH, Ytrebo LM, Olsen R, Revhaug A, Smedsrod B (2003) Comp Hepatol 2:1

    Article  Google Scholar 

  8. Willekens FLA, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Döpp YAM, Bos AGvd, Bosman GJCGM, Berkel TJCv (2005) Blood 105:2141

    Article  CAS  Google Scholar 

  9. Behnia K, Bhatia S, Jastromb N, Balis U, Sullivan S, Yarmush ML, Toner M (2000) Tissue Eng 6:467

    Article  CAS  Google Scholar 

  10. Grattagliano I, Portincasa P, Palmieri VO, Palasciano G (2002) Annal Hepatol 1:162

    Google Scholar 

  11. Ankoma-Sey V (1999) News Physiol Sci 14:149

    CAS  Google Scholar 

  12. Michalopoulos GK, DeFrances MC (1997) Science 276:60

    Article  CAS  Google Scholar 

  13. Popovic JR, Kozak LJ (2000) Vital Health Stat 13

    Google Scholar 

  14. Yarmush ML, Toner M, Dunn JCY, Rotem A, Hubel A, Tompkins RG (1992) Annal NY Acad Sci 665:238

    Article  CAS  Google Scholar 

  15. Tsiaoussis J, Newsome PN, Nelson LJ, Hayes PC, Plevris JN (2001) Liver Tansplant 7:2

    Article  CAS  Google Scholar 

  16. Matsumoto K, Yoshitomi H, Rossant J, Zaret KS (2001) Science 297:559

    Article  Google Scholar 

  17. Fondevila C, Busuttil RW, Kupiec-Weglinski JW (2003) Exp Mol Pathol 74:86

    Article  CAS  Google Scholar 

  18. Neubauer K, Saile B, Ramadori G (2001) Can J Gastroenterol 15:187

    CAS  Google Scholar 

  19. Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T, Olson WC (2003) PNAS 100:4498

    Article  CAS  Google Scholar 

  20. Jayaraman A, Yarmush ML, Roth CM (2005) Tissue Eng 11:50

    Article  CAS  Google Scholar 

  21. Jung J, Zheng M, Goldfarb M, Zaret KS (1999) Science 284:1998

    Article  CAS  Google Scholar 

  22. Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M, Gherardi E, Birchmeler C (1995) Nature 373:699

    Article  CAS  Google Scholar 

  23. Lemaigre F, Zaret KS (2004) Curr Opin Genet Dev 14:582

    Article  CAS  Google Scholar 

  24. Sosa-Pineda B, Wigle JT, Oliver G (2000) Nat Genet 25:254

    Article  CAS  Google Scholar 

  25. Lammert E, Cleaver O, Melton D (2001) Science 294:564

    Article  CAS  Google Scholar 

  26. McCuskey RS, Ekataksin W, LeBouton AV, Nishida J, McCuskey MK, McDonnell D, Williams C, Bethea NW, Dvorak B, Koldovsky O (2003) Anatom Rec Part A 275A:1019–1030

    Google Scholar 

  27. Martinez-Hernandez A, Amenta PS (1995) FASEB J 9:1401

    CAS  Google Scholar 

  28. Allen JW, Bhatia SN (2003) Biotechnol Bioeng 82:253

    Article  CAS  Google Scholar 

  29. Haussinger D, Lamers WH, Moorman AF (1992) Enzyme 46:72

    CAS  Google Scholar 

  30. Jungermann K (1992) Diabete Metab 18:81

    CAS  Google Scholar 

  31. Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA (1992) Hepatology 15:1198

    Article  CAS  Google Scholar 

  32. Bouwens L, Bleser PD, Vanderkerken K, Geerts B, Wisse E (1992) Enzyme 46:155

    CAS  Google Scholar 

  33. Braet F, Wisse E (2002) Comparat Hepatol 1:1

    Article  Google Scholar 

  34. Morin O, Goulet F, Normand C (1988) Rev Sobre Biol Cel 15:1

    CAS  Google Scholar 

  35. Gores GJ, Kost LJ, LaRusso NF (1986) Hepatology 6:511

    Article  CAS  Google Scholar 

  36. Lee K, Berthiaume F, Stephanopoulos GN, Yarmush DM, Yarmush ML (2000) Metab Eng 2:312

    Article  CAS  Google Scholar 

  37. Tavill AS, East AG, Black EG, Nadkarni D, Hoffenberg E (1972) Ciba Found Symp 9:155

    CAS  Google Scholar 

  38. Palmen NG, Evelo CT, Borm PJ, Henderson PT (1993) Hum Exp Toxicol 12:127

    Article  CAS  Google Scholar 

  39. McKindley DS, Chichester C, Raymond R (1999) Shock 12:468

    Article  CAS  Google Scholar 

  40. Gordon AH, Humphrey JH (1960) Biochem J 75:240

    CAS  Google Scholar 

  41. Burke WT (1960) Biochem Biophys Res Commun 3:525

    Article  CAS  Google Scholar 

  42. Zhao P, Kalhorn TF, Slattery JT (2002) Hepatology 36:326

    Article  CAS  Google Scholar 

  43. Martin H, Sarsat JP, Lerche-Langrand C, Housset C, Balladur P, Toutain H, Albaladejo V (2002) Cell Biol Toxicol 18:73

    Article  CAS  Google Scholar 

  44. Fisher RL, Ulreich JB, Nakazato PZ, Brendel K (2001) Toxicol Method 11:59

    Article  CAS  Google Scholar 

  45. Lerche-Langrand C, Toutain HJ (2000) Toxicology 153:221

    Article  CAS  Google Scholar 

  46. Neyrinck A, Eeckhoudt SL, Meunier CJ, Pampfer S, Taper HS, Verbeeck RK, Delzenne N (1999) Life Sci 65:2851

    Article  CAS  Google Scholar 

  47. Olinga P, Hof IH, Merema MT, Smit M, Jager MHd, Swart PJ, Slooff MJ, Meijer DK, Groothuis GM (2001) J Pharmacol Toxicol Method 45:55

    Article  CAS  Google Scholar 

  48. Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS (1996) Gene Dev 10:1670

    Article  CAS  Google Scholar 

  49. Seglen PO (1976) Method Cell Biol 13:29

    Article  CAS  Google Scholar 

  50. Strain AJ (1994) Gut 35:433

    Article  CAS  Google Scholar 

  51. Dunn JCY, Tompkins RG, Yarmush ML (1991) Biotechnol Prog 7:237

    Article  CAS  Google Scholar 

  52. Koide N, Shinji T, Tanabe T, Asano K, Kawaguchi M, Sakaguchi K, Koide Y, Mori M, Tsuji T (1989) Biochem Biophys Res Commun 161:385

    Article  CAS  Google Scholar 

  53. Abu-Absi SF, Friend JR, Hansen LK, Hu W-S (2002) Exp Cell Res 274:56

    Article  CAS  Google Scholar 

  54. Yarmush ML, Toner M, Dunn JC, Rotem A, Hubel A, Tompkins RG (1992) Ann NY Acad Sci 665:238

    Article  CAS  Google Scholar 

  55. Hamilton GA, Westmorel C, George AE (2001) In Vitro Cell Dev Biol Animal 37:656

    Article  CAS  Google Scholar 

  56. Dunn JC, Yarmush ML, Koebe HG, Tompkins RG (1989) FASEB J 3:174

    CAS  Google Scholar 

  57. Dunn JC, Tompkins RG, Yarmush ML (1992) J Cell Biol 116:1043

    Article  CAS  Google Scholar 

  58. Moghe PV, Berthiaume F, Ezzell RM, Toner M, Tompkins RG, Yarmush ML (1996) Biomaterials 17:373

    Article  CAS  Google Scholar 

  59. Berthiaume F, Moghe PV, Toner M, Yarmush ML (1996) FASEB J 10:1471

    CAS  Google Scholar 

  60. Moghe PV, Coger RN, Toner M, Yarmush ML (1997) Biotechnol Bioeng 56:706

    Article  CAS  Google Scholar 

  61. Landry J, Bernier D, Ouellet C, Goyette R, Marceau N (1985) J Cell Biol 101:914

    Article  CAS  Google Scholar 

  62. Schuetz EG, Li D, Omiecinski CJ, Muller-Eberhard U, Kleinman HK, Elswick B, Guzelian PS (1988) J Cell Physiol 134:309

    Article  CAS  Google Scholar 

  63. Peshwa MV, Wu FJ, Sharp HL, Cerra FB, Hu W-S (1996) In Vitro Cell Dev Biol Animal 32:197

    Article  CAS  Google Scholar 

  64. Wu FJ, Friend JR, Remmel RP, Cerra FB, Hu W-S (1999) Cell Transplant 8:233

    CAS  Google Scholar 

  65. Strain AJ (1999) Hepatology 29:288

    Article  CAS  Google Scholar 

  66. Mitaka T, Sato F, Mizuguchi T, Yokono T, Mochizuki Y (1999) Hepatology 29:111

    Article  CAS  Google Scholar 

  67. Mitaka T (2002) J Hepatobiliary Pancreat Surg 9:697–703

    Article  Google Scholar 

  68. Harada K, Mitaka T, Miyamoto S, Sugimoto S, Ikeda S, Takeda H, Mochizuki Y, Hirata K (2003) J Hepatol 39:716–723

    Article  CAS  Google Scholar 

  69. Michalopoulos GK, Bowen WC, Zajac VF, Stolz DB, Watkins S, Kostrubsky V, Strom SC (1999) Hepatology 29:90

    Article  CAS  Google Scholar 

  70. Michalopoulos GK, Bowen WC, Mule K, Stolz DB (2001) Am J Pathol 159:1877–1887

    Article  CAS  Google Scholar 

  71. Bhatia SN, Yarmush ML, Toner M (1997) J Biomed Mater Res 34:189

    Article  CAS  Google Scholar 

  72. Bhatia SN, Balis UJ, Yarmush ML, Toner M (1999) FASEB J 13:1883

    CAS  Google Scholar 

  73. Khetani SR, Szulgit G, Rio JAD, Barlow C, Bhatia SN (2004) Hepatology 40:545

    Article  CAS  Google Scholar 

  74. Morin O, Normand C (1986) J Cell Physiol 129:103

    Article  CAS  Google Scholar 

  75. Goulet F, Normand C, Morin O (1988) Hepatology 8:1010

    Article  CAS  Google Scholar 

  76. LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber H-P, Hillan KJ, Ferrara N (2003) Science 299:890

    Article  CAS  Google Scholar 

  77. Nahmias Y, Schwartz RE, Wei-Shou H, Verfaillie CM, Odde DJ (2006) Tissue Eng 12:1627

    Article  CAS  Google Scholar 

  78. Nahmias YK, Odde DJ (2002) IEEE J Quantum Electron 38:131

    Article  CAS  Google Scholar 

  79. Nahmias YK, Gao BZ, Odde DJ (2004) Appl Opt 43:3999

    Article  Google Scholar 

  80. Nahmias Y, Schwartz RE, Verfaillie CM, Odde DJ (2005) Biotechnol Bioeng 92:129

    Article  CAS  Google Scholar 

  81. Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML (2006) Hepatology 43:257

    Article  CAS  Google Scholar 

  82. Jaeschke H, Farhood A (1991) Am J Physiol 260:G355

    CAS  Google Scholar 

  83. James LP, Mayeux PR, Hinson JA (2003) Drug Metabol Disp 31:1499

    Article  CAS  Google Scholar 

  84. Hoebe KH, Witkamp RF, Fink-Gremmels J, Miert ASV, Monshouwer M (2001) Am J Physiol Gastrointest Liver Physiol 280:G720

    CAS  Google Scholar 

  85. Milosevic N, Schawalder H, Maier P (1999) Eur J Pharmacol 368:75

    Article  CAS  Google Scholar 

  86. Tilles AW, Baskaran H, Roy P, Yarmush ML, Toner M (2001) Biotechnol Bioeng 73:379

    Article  CAS  Google Scholar 

  87. Balis UJ, Behnia K, Dwarakanath B, Bhatia SN, Sullivan SJ, Yarmush ML, Toner M (1999) Metabol Eng 1:49

    Article  CAS  Google Scholar 

  88. Foy BD, Rotem A, Toner M, Tompkins RG, Yarmush ML (1994) Cell Transplant 3:515

    CAS  Google Scholar 

  89. Lemasters JJ (2001) In: Arias IM (ed) The liver: biology and pathobiology. Lippincott Williams & Wilkins, Philadelphia, p 257

    Google Scholar 

  90. Bhatia SN, Toner M, Foy BD, Rotem A, O'Neil KM, Tompkins RG, Yarmush ML (1996) J Cell Eng 1:125

    Google Scholar 

  91. Fariss MW (1990) Free Radic Biol Med 9:333

    Article  CAS  Google Scholar 

  92. King AT, Mulligan BJ, Lowe KC (1989) Nat Biotechnol 7:1037

    CAS  Google Scholar 

  93. Gordon JE, Dare MR, Palmer AF (2005) Biotechnol Prog 21:1700

    Article  CAS  Google Scholar 

  94. Rappaport C, Rensch Y, Abbasi M, Kempe M, Rocaboy C, Gladysz J, Trujillo EM (2002) Biotechniques 32:142

    CAS  Google Scholar 

  95. Rotem A, Toner M, Bhatia S, Foy BD, Tompkins RG, Yarmush ML (1994) Biotechnol Bioeng 43:654

    Article  CAS  Google Scholar 

  96. Williams GM, Bermudez E, Scaramuzzino D (1977) In Vitro 13:809

    Article  CAS  Google Scholar 

  97. Zupke CA, Stefanovich P, Berthiaume F, Yarmush ML (1998) Biotechnol Bioeng 58:222

    Article  CAS  Google Scholar 

  98. Matthew HWT, Sternberg J, Stefanovich P, Morgan JR, Toner M, Tompkins RG, Yarmush ML (1996) Biotechnol Bioeng 51:100

    Article  CAS  Google Scholar 

  99. Chan C, Berthiaume F, Washizu J, Toner M, Yarmush ML (2002) Biotechnol Bioeng 78:753

    Article  CAS  Google Scholar 

  100. Andersson H, Berg Avd (2004) Lab Chip 4:98

    Article  CAS  Google Scholar 

  101. Kataropoulou M, Henderson C, Grant MH (2005) Tissue Engineering 11:1263

    Article  CAS  Google Scholar 

  102. Park J, Berthiaume F, Toner M, Yarmush ML, Tilles AW (2005) Biotechnol Bioeng 90:632

    Article  CAS  Google Scholar 

  103. Khademhosseini A, Yeh J, Eng G, Karp J, Kaji H, Borenstein J, Farokhzad OC, Langer R (2005) Lab Chip 5:1380

    Article  CAS  Google Scholar 

  104. Allen JW, Khetani SR, Bhatia SN (2005) Toxicol Sci 84:110

    Article  CAS  Google Scholar 

  105. Strain AJ, Neuberger JM (2002) Science 295:1005

    Article  CAS  Google Scholar 

  106. Griffith LG, Naughton G (2002) Science 295:1009

    Article  CAS  Google Scholar 

  107. Ohshima N, Yanagi K, Miyoshi H (1997) Artif Organs 21:1169

    Article  CAS  Google Scholar 

  108. Murtas S, Capuani G, Dentini M, Manetti C, Masci G, Massimi M, Miccheli A, Crescenzi V (2005) J Biomater Sci Polym Ed 16:829

    Article  CAS  Google Scholar 

  109. Li AP, Barker G, Beck D, Colburn S, Monsell R, Pellegrin C (1993) In Vitro Cell Dev Biol 29A:249

    Google Scholar 

  110. Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upadhyaya A, Kurzawski P, Wack KE, Stolz DB, Kamm R, Griffith LG (2002) Biotechnol Bioeng 78:257

    Article  CAS  Google Scholar 

  111. Griffith LG, Swartz MA (2006) Nat Rev Mol Cell Biol 7:211

    Article  CAS  Google Scholar 

  112. Powers MJ, Janigian DM, Wack KE, Baker CS, Stolz DB, Griffith LG (2002) Tissue Eng 8:499

    Article  Google Scholar 

  113. Sivaraman A, Leach JK, Townsend S, Iida T, Hogan BJ, Stolz DB, Fry R, Samson LD, Tannenbaum SR, Griffith LG (2005) Curr Drug Metab 6:569

    Article  CAS  Google Scholar 

  114. Bhatia SN, Balis UJ, Yarmush ML, Toner M (1998) J Biomater Sci Polym Ed 9:1137

    Article  CAS  Google Scholar 

  115. Kan P, Miyoshi H, Yanagi K, Ohshima N (1998) ASAIO 44: M441

    Google Scholar 

  116. Monga SPS, Hout MS, Baun MJ, Micsenyi A, Muller P, Tummalapalli L, Ranade AR, Luo J-H, Strom SC, Gerlach JC (2005) Am J Pathol 167:1279

    Article  CAS  Google Scholar 

  117. Saito M, Matsuura T, Masaki T, Maehashi H, Shimizu K, Hataba Y, Iwahori T, Suzuki T, Braet F (2006) World J Gastroenterol 12:1881

    CAS  Google Scholar 

  118. Benyon RC, Iredale JP (2000) Gut 46:443

    Article  CAS  Google Scholar 

  119. Bataller R, Brenner DA (2005) J Clin Invest 115:209

    CAS  Google Scholar 

  120. Friedman SL, Bansal MB (2006) Hepatology 43:S82

    Article  CAS  Google Scholar 

  121. Albanis E, Friedman SL (2006) Am J Transplant 6:12

    Article  CAS  Google Scholar 

  122. Prosser CC, Yen RD, Wu J (2006) World J Gastroenterol 12:509

    CAS  Google Scholar 

  123. Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky J-M (2004) Hepatology 39:5–19

    Article  CAS  Google Scholar 

  124. Guidotti LG, Chisari FV (2006) Ann Rev Pathol Mech Dis 1:23–61

    Article  CAS  Google Scholar 

  125. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Krausslich HG, Mizokami M, Bartenschlager R, Liang TJ (2005) Nat Med 11:791

    Article  CAS  Google Scholar 

  126. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM (2005) Science 309:623

    Article  CAS  Google Scholar 

  127. Ujhazy P, Kipp H, Misra S, Wakabayashi Y, Arias IM (2001) In: Arias IM (ed) The Liver, Biology and Pathobiology. Lippincott Williams & Wilkins, Philadelphia, p 361

    Google Scholar 

  128. Clouzeau-Girard H, Guyot C, Combe C, Moronvalle-Halley V, Housset C, Lamireau T, Rosenbaum J, Desmoulière A (2006) Lab Invest 86:275

    Article  CAS  Google Scholar 

  129. Tilles AW, Berthiaume F, Yarmush ML, Tompkins RG, Toner M (2002) J Hepatobiliary Pancreat Surg 9:686

    Article  Google Scholar 

  130. Thompson DM, King KR, Wieder KJ, Toner M, Yarmush ML, Jayaraman A (2004) Anal Chem 76:4098

    Article  CAS  Google Scholar 

  131. Wieder KJ, King KR, Thompson DM, Zia C, Yarmush ML, Jayaraman A (2005) Biomed Microdev 7:213

    Article  Google Scholar 

  132. Davidson AJ, Zon LI (2003) Science 299:835

    Article  CAS  Google Scholar 

  133. Sugimachi K, Sosef MN, Baust JM, Fowler A, Tompkins RG, Toner M (2004) Cell Transplant 13:187

    Google Scholar 

  134. Bhandari RN, Riccalton LA, Lewis AL, Fry JR, Hammond AH, Tendler SJ, Shakesheff KM (2001) Tissue Eng 7:345

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Institutes of Health (R01DK43371 and P41ED002503) and the Shriners Hospitals for Children.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin L. Yarmush .

Editor information

Kyongbum Lee David Kaplan

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Nahmias, Y., Berthiaume, F., Yarmush, M.L. (2006). Integration of Technologies for Hepatic Tissue Engineering. In: Lee, K., Kaplan, D. (eds) Tissue Engineering II. Advances in Biochemical Engineering/Biotechnology, vol 103. Springer, Berlin, Heidelberg . https://doi.org/10.1007/10_029

Download citation

Publish with us

Policies and ethics