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.
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References
Zakim D, Boyer T (1996) Hepatology: A textbook of liver disease. W.B. Saunders, Philadelphia
Desmet VJ (2001) In: Arias IM (ed) The liver, biology and pathobiology. Lippincott Williams & Wilkins, Philadelphia, p 3
Taub R (2004) Nat Rev Mol Cell Biol 5:836
Dahn MS, Lange MP, Berberoglu ED (1996) Shock 6:52
Lee K, Berthiaume F, Stephanopoulos GN, Yarmush ML (2003) Biotechnol Bioeng 83:400
Ramadori G, Christ B (1999) Semin Liver Dis 19:141
Nedredal GI, Elvevold KH, Ytrebo LM, Olsen R, Revhaug A, Smedsrod B (2003) Comp Hepatol 2:1
Willekens FLA, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Döpp YAM, Bos AGvd, Bosman GJCGM, Berkel TJCv (2005) Blood 105:2141
Behnia K, Bhatia S, Jastromb N, Balis U, Sullivan S, Yarmush ML, Toner M (2000) Tissue Eng 6:467
Grattagliano I, Portincasa P, Palmieri VO, Palasciano G (2002) Annal Hepatol 1:162
Ankoma-Sey V (1999) News Physiol Sci 14:149
Michalopoulos GK, DeFrances MC (1997) Science 276:60
Popovic JR, Kozak LJ (2000) Vital Health Stat 13
Yarmush ML, Toner M, Dunn JCY, Rotem A, Hubel A, Tompkins RG (1992) Annal NY Acad Sci 665:238
Tsiaoussis J, Newsome PN, Nelson LJ, Hayes PC, Plevris JN (2001) Liver Tansplant 7:2
Matsumoto K, Yoshitomi H, Rossant J, Zaret KS (2001) Science 297:559
Fondevila C, Busuttil RW, Kupiec-Weglinski JW (2003) Exp Mol Pathol 74:86
Neubauer K, Saile B, Ramadori G (2001) Can J Gastroenterol 15:187
Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T, Olson WC (2003) PNAS 100:4498
Jayaraman A, Yarmush ML, Roth CM (2005) Tissue Eng 11:50
Jung J, Zheng M, Goldfarb M, Zaret KS (1999) Science 284:1998
Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M, Gherardi E, Birchmeler C (1995) Nature 373:699
Lemaigre F, Zaret KS (2004) Curr Opin Genet Dev 14:582
Sosa-Pineda B, Wigle JT, Oliver G (2000) Nat Genet 25:254
Lammert E, Cleaver O, Melton D (2001) Science 294:564
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
Martinez-Hernandez A, Amenta PS (1995) FASEB J 9:1401
Allen JW, Bhatia SN (2003) Biotechnol Bioeng 82:253
Haussinger D, Lamers WH, Moorman AF (1992) Enzyme 46:72
Jungermann K (1992) Diabete Metab 18:81
Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA (1992) Hepatology 15:1198
Bouwens L, Bleser PD, Vanderkerken K, Geerts B, Wisse E (1992) Enzyme 46:155
Braet F, Wisse E (2002) Comparat Hepatol 1:1
Morin O, Goulet F, Normand C (1988) Rev Sobre Biol Cel 15:1
Gores GJ, Kost LJ, LaRusso NF (1986) Hepatology 6:511
Lee K, Berthiaume F, Stephanopoulos GN, Yarmush DM, Yarmush ML (2000) Metab Eng 2:312
Tavill AS, East AG, Black EG, Nadkarni D, Hoffenberg E (1972) Ciba Found Symp 9:155
Palmen NG, Evelo CT, Borm PJ, Henderson PT (1993) Hum Exp Toxicol 12:127
McKindley DS, Chichester C, Raymond R (1999) Shock 12:468
Gordon AH, Humphrey JH (1960) Biochem J 75:240
Burke WT (1960) Biochem Biophys Res Commun 3:525
Zhao P, Kalhorn TF, Slattery JT (2002) Hepatology 36:326
Martin H, Sarsat JP, Lerche-Langrand C, Housset C, Balladur P, Toutain H, Albaladejo V (2002) Cell Biol Toxicol 18:73
Fisher RL, Ulreich JB, Nakazato PZ, Brendel K (2001) Toxicol Method 11:59
Lerche-Langrand C, Toutain HJ (2000) Toxicology 153:221
Neyrinck A, Eeckhoudt SL, Meunier CJ, Pampfer S, Taper HS, Verbeeck RK, Delzenne N (1999) Life Sci 65:2851
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
Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS (1996) Gene Dev 10:1670
Seglen PO (1976) Method Cell Biol 13:29
Strain AJ (1994) Gut 35:433
Dunn JCY, Tompkins RG, Yarmush ML (1991) Biotechnol Prog 7:237
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
Abu-Absi SF, Friend JR, Hansen LK, Hu W-S (2002) Exp Cell Res 274:56
Yarmush ML, Toner M, Dunn JC, Rotem A, Hubel A, Tompkins RG (1992) Ann NY Acad Sci 665:238
Hamilton GA, Westmorel C, George AE (2001) In Vitro Cell Dev Biol Animal 37:656
Dunn JC, Yarmush ML, Koebe HG, Tompkins RG (1989) FASEB J 3:174
Dunn JC, Tompkins RG, Yarmush ML (1992) J Cell Biol 116:1043
Moghe PV, Berthiaume F, Ezzell RM, Toner M, Tompkins RG, Yarmush ML (1996) Biomaterials 17:373
Berthiaume F, Moghe PV, Toner M, Yarmush ML (1996) FASEB J 10:1471
Moghe PV, Coger RN, Toner M, Yarmush ML (1997) Biotechnol Bioeng 56:706
Landry J, Bernier D, Ouellet C, Goyette R, Marceau N (1985) J Cell Biol 101:914
Schuetz EG, Li D, Omiecinski CJ, Muller-Eberhard U, Kleinman HK, Elswick B, Guzelian PS (1988) J Cell Physiol 134:309
Peshwa MV, Wu FJ, Sharp HL, Cerra FB, Hu W-S (1996) In Vitro Cell Dev Biol Animal 32:197
Wu FJ, Friend JR, Remmel RP, Cerra FB, Hu W-S (1999) Cell Transplant 8:233
Strain AJ (1999) Hepatology 29:288
Mitaka T, Sato F, Mizuguchi T, Yokono T, Mochizuki Y (1999) Hepatology 29:111
Mitaka T (2002) J Hepatobiliary Pancreat Surg 9:697–703
Harada K, Mitaka T, Miyamoto S, Sugimoto S, Ikeda S, Takeda H, Mochizuki Y, Hirata K (2003) J Hepatol 39:716–723
Michalopoulos GK, Bowen WC, Zajac VF, Stolz DB, Watkins S, Kostrubsky V, Strom SC (1999) Hepatology 29:90
Michalopoulos GK, Bowen WC, Mule K, Stolz DB (2001) Am J Pathol 159:1877–1887
Bhatia SN, Yarmush ML, Toner M (1997) J Biomed Mater Res 34:189
Bhatia SN, Balis UJ, Yarmush ML, Toner M (1999) FASEB J 13:1883
Khetani SR, Szulgit G, Rio JAD, Barlow C, Bhatia SN (2004) Hepatology 40:545
Morin O, Normand C (1986) J Cell Physiol 129:103
Goulet F, Normand C, Morin O (1988) Hepatology 8:1010
LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber H-P, Hillan KJ, Ferrara N (2003) Science 299:890
Nahmias Y, Schwartz RE, Wei-Shou H, Verfaillie CM, Odde DJ (2006) Tissue Eng 12:1627
Nahmias YK, Odde DJ (2002) IEEE J Quantum Electron 38:131
Nahmias YK, Gao BZ, Odde DJ (2004) Appl Opt 43:3999
Nahmias Y, Schwartz RE, Verfaillie CM, Odde DJ (2005) Biotechnol Bioeng 92:129
Nahmias Y, Casali M, Barbe L, Berthiaume F, Yarmush ML (2006) Hepatology 43:257
Jaeschke H, Farhood A (1991) Am J Physiol 260:G355
James LP, Mayeux PR, Hinson JA (2003) Drug Metabol Disp 31:1499
Hoebe KH, Witkamp RF, Fink-Gremmels J, Miert ASV, Monshouwer M (2001) Am J Physiol Gastrointest Liver Physiol 280:G720
Milosevic N, Schawalder H, Maier P (1999) Eur J Pharmacol 368:75
Tilles AW, Baskaran H, Roy P, Yarmush ML, Toner M (2001) Biotechnol Bioeng 73:379
Balis UJ, Behnia K, Dwarakanath B, Bhatia SN, Sullivan SJ, Yarmush ML, Toner M (1999) Metabol Eng 1:49
Foy BD, Rotem A, Toner M, Tompkins RG, Yarmush ML (1994) Cell Transplant 3:515
Lemasters JJ (2001) In: Arias IM (ed) The liver: biology and pathobiology. Lippincott Williams & Wilkins, Philadelphia, p 257
Bhatia SN, Toner M, Foy BD, Rotem A, O'Neil KM, Tompkins RG, Yarmush ML (1996) J Cell Eng 1:125
Fariss MW (1990) Free Radic Biol Med 9:333
King AT, Mulligan BJ, Lowe KC (1989) Nat Biotechnol 7:1037
Gordon JE, Dare MR, Palmer AF (2005) Biotechnol Prog 21:1700
Rappaport C, Rensch Y, Abbasi M, Kempe M, Rocaboy C, Gladysz J, Trujillo EM (2002) Biotechniques 32:142
Rotem A, Toner M, Bhatia S, Foy BD, Tompkins RG, Yarmush ML (1994) Biotechnol Bioeng 43:654
Williams GM, Bermudez E, Scaramuzzino D (1977) In Vitro 13:809
Zupke CA, Stefanovich P, Berthiaume F, Yarmush ML (1998) Biotechnol Bioeng 58:222
Matthew HWT, Sternberg J, Stefanovich P, Morgan JR, Toner M, Tompkins RG, Yarmush ML (1996) Biotechnol Bioeng 51:100
Chan C, Berthiaume F, Washizu J, Toner M, Yarmush ML (2002) Biotechnol Bioeng 78:753
Andersson H, Berg Avd (2004) Lab Chip 4:98
Kataropoulou M, Henderson C, Grant MH (2005) Tissue Engineering 11:1263
Park J, Berthiaume F, Toner M, Yarmush ML, Tilles AW (2005) Biotechnol Bioeng 90:632
Khademhosseini A, Yeh J, Eng G, Karp J, Kaji H, Borenstein J, Farokhzad OC, Langer R (2005) Lab Chip 5:1380
Allen JW, Khetani SR, Bhatia SN (2005) Toxicol Sci 84:110
Strain AJ, Neuberger JM (2002) Science 295:1005
Griffith LG, Naughton G (2002) Science 295:1009
Ohshima N, Yanagi K, Miyoshi H (1997) Artif Organs 21:1169
Murtas S, Capuani G, Dentini M, Manetti C, Masci G, Massimi M, Miccheli A, Crescenzi V (2005) J Biomater Sci Polym Ed 16:829
Li AP, Barker G, Beck D, Colburn S, Monsell R, Pellegrin C (1993) In Vitro Cell Dev Biol 29A:249
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
Griffith LG, Swartz MA (2006) Nat Rev Mol Cell Biol 7:211
Powers MJ, Janigian DM, Wack KE, Baker CS, Stolz DB, Griffith LG (2002) Tissue Eng 8:499
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
Bhatia SN, Balis UJ, Yarmush ML, Toner M (1998) J Biomater Sci Polym Ed 9:1137
Kan P, Miyoshi H, Yanagi K, Ohshima N (1998) ASAIO 44: M441
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
Saito M, Matsuura T, Masaki T, Maehashi H, Shimizu K, Hataba Y, Iwahori T, Suzuki T, Braet F (2006) World J Gastroenterol 12:1881
Benyon RC, Iredale JP (2000) Gut 46:443
Bataller R, Brenner DA (2005) J Clin Invest 115:209
Friedman SL, Bansal MB (2006) Hepatology 43:S82
Albanis E, Friedman SL (2006) Am J Transplant 6:12
Prosser CC, Yen RD, Wu J (2006) World J Gastroenterol 12:509
Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky J-M (2004) Hepatology 39:5–19
Guidotti LG, Chisari FV (2006) Ann Rev Pathol Mech Dis 1:23–61
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
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
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
Clouzeau-Girard H, Guyot C, Combe C, Moronvalle-Halley V, Housset C, Lamireau T, Rosenbaum J, Desmoulière A (2006) Lab Invest 86:275
Tilles AW, Berthiaume F, Yarmush ML, Tompkins RG, Toner M (2002) J Hepatobiliary Pancreat Surg 9:686
Thompson DM, King KR, Wieder KJ, Toner M, Yarmush ML, Jayaraman A (2004) Anal Chem 76:4098
Wieder KJ, King KR, Thompson DM, Zia C, Yarmush ML, Jayaraman A (2005) Biomed Microdev 7:213
Davidson AJ, Zon LI (2003) Science 299:835
Sugimachi K, Sosef MN, Baust JM, Fowler A, Tompkins RG, Toner M (2004) Cell Transplant 13:187
Bhandari RN, Riccalton LA, Lewis AL, Fry JR, Hammond AH, Tendler SJ, Shakesheff KM (2001) Tissue Eng 7:345
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This work was supported by grants from the National Institutes of Health (R01DK43371 and P41ED002503) and the Shriners Hospitals for Children.
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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
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