우리 인체의 장기 중 간(liver)은 생존에 그 어느 장기보다도 중요한 역할을 담당하는 장기로서 여러 가지 원인으로 인하여 갑자기 간의 기능이 상실된 환자에게는 간이식만이 유일한 대안이다. 간세포를 이용한 체외 순환형 간 보조 장치(생인공간, bioartificial liver)는 최근 유일하게 전격성 간부전 환자의 생존율 증대 효과가 검증되었고 간이식이나 환자 자신의 간 재생으로의 생명 연장 교량 역할을 효과적으로 수행할 수 있을 것으로 기대되고 있다. 본 논문에서는 생인공간의 개념과 임상시험 중인 대표적인 생인공간 시스템 현황에 대해서 공학적 관점 위주로 소개하고 향후 이 분야에 대한 연구전망에 대하여 서술하였다.

The liver is mutifunctional vital organ for healthy survival and orthotopic liver transplatation is the only definitive therapy for patients with acute or fulminant failure (FHF) so far. Bioartificial liver, a hepatocyte-based extracorporeal liver support system, enhanced the survival rates of patients with FHF and expected to act as a bridge to provide the extension of survival time until a donor organ becomes available for transplantation or their own liver can be regenerated. In this paper, we introduce concepts of bioartificial liver and review representative bioartificial liver systems in clinical trial s with engineering issue. Finally we describe future perspectives of bioartificial liver.

Bioartificial Liver Fulminant Hepatic Failure Hepatocyte Spheroid Hepatic Stem Cell Hepatocyte Bioreactor

Langer R, Vacanti JP, Science, 260, 920 (1993) 
Stocum DL, Semin. Cell Dev. Biol., 10(4), 433 (1999) 
Sussman NL, Kelly JH, Artificial Organs, 17, 27 (1993)
Mito M, Artificial Organs., 10, 214 (1986)
Leigh JP, Bowlus CL, Leistikow BN, Schenker M, Arch. Int. Med., 161, 2231 (2001) 
Kamlot A, Rozga J, Watanabe FD, Demetriou AA, Biotechnol. Bioeng., 50(4), 382 (1996) 
Sussman NL, Kelly JH, Hepatology, 17, 1163 (1993) 
Howard RB, J. Cell Biol., 36, 675 (1967) 
Berry MN, Friend DS, J. Cell. Biol., 43, 506 (1969) 
Seglen PO, Method Cell Biol., 13, 29 (1978)
Kasai S, Muto M, "Cryopreserved Hepatocytes for Fluid Bed Ractors," In "Artificial Liver Support," edited by Brunner G. and Mito M., 2nd ed., Springer-Verlag, 251-260 (1992)
Landry J, Bernier D, Ouellet C, Goyette R, Marceau N, J. Cell Biol., 101, 914 (1985) 
Koide N, Skaguchi K, Koide Y, Asano K, Kawaguchi M, Matsushima H, Takenami T, Shinji T, Mori M, Tsuji T, Exp. Cell. Res., 186, 227 (1990) 
Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA, Hepatology, 15, 1198 (1992)
Bissell DM, Arenson DM, Maher JJ, Roll FJ, J. Clin. Invest., 79, 801 (1987)
Dunn JCY, Tompkins RG, Yarmush ML, Biotechnol. Prog., 7, 237 (1991) 
Shimbara N, Atawa R, Takashina M, Tanaka K, Ichihara A, Cytotechnology, 21, 31 (1996) 
Surapaneni S, Pryor T, Klein MD, Matthew HWT, ASAIO J., 43, M848 (1997)
Matsushita T, Ijima H, Koide N, Funatsu K, Appl. Microbiol. Biotechnol., 36, 324 (1991)
Wu FJ, Friend JR, Hsiao CC, Zilliox MJ, Ko WJ, Cerra FB, Hu WS, Biotechnol. Bioeng., 50(4), 404 (1996) 
Wanson JC, Mosselmans R, Brouwer A, Knook DC, Biol. Cell., 56, 7 (1979)
Michalopoulos G, Russel F, Biles C, Vitro, 15, 796 (1979)
Clement B, Guguen-Guillouzo C, Campion JP, Glaise D, Bourel M, Guillouzo A, Hepatology, 4, 373 (1984)
Guguen-Guillouzo C, Clement B, Baffet G, Beaumont C, MorelChany E, Glaise D, Exp. Cell Res., 143, 47 (1983) 
Guguen-Guillouzo C, Clement B, Baffet G, Begue JM, Glaise D, Guillouzo A, "Human Adult Hepatocytes: Isolation and Maintenance at High Levels of Specific Functions in a Co-Culture System. Isolation, Characterization, and use of Hepatocytes," Harris, R.A. and Cornell, N.W., Eds., Elsevier, New York, 105-110 (1983)
Guillouzo A, Morel F, Ratanasavanh D, Chesne C, Guguen-Guillouzo C, Toxic. Vitro, 4, 415 (1990) 
Landry J, Bernier D, Ouellet C, Goyette R, Marceau N, J. Cell Biol., 101, 914 (1985) 
Goulet F, Morin O, Hepatology, 5, 1010 (1988)
Naughton BA, Sanroman WJ, Sibanda B, Weintraub JP, Kamali V, Biotechnol. Bioeng., 43(8), 810 (1994) 
Donato MT, Castell JV, Gomez-Lechon MJ, Cytotechnology, 17, 45 (1995) 
Hui T, Rozga J, Demetriou AA, J. Hepatobiliary Pancreat. Surg., 8, 1 (2001) 
Watanabe FD, Mullon CJ, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi S, Khalili T, Arnaout W, Shackleton CR, Rozga J, Solomon B, Demetriou AA, Annu. Surg., 225, 481 (1997)
Hu WS, Friend JR, Wu FJ, Sielaff T, Peshwa MV, Lazer A, Nygerg SL, Remmel RP, Cerra FB, Cytotechnology, 23, 29 (1997) 
Flendrig LM, Maas MAW, Daalhuisen J, Ladiges NCJJ, LaSoe JW, TeVelde AA, Chamuleau RAFM, Int. J. Artificial Organs, 21, 542 (1998)
Dixit V, Gitnick G, Scand. J. Gastroenterol., 220, 101 (1996)
Gion T, Shimada M, Shirabe K, Nakazawa K, Ijima H, Matsushita T, Funatsu K, Sugimachi K, J. Surg. Res., 82, 131 (1999) 
Strain SJ, Neuberger JM, Science, 295, 1005 (2002) 
Watanabe FD, Mullon CJP, Hewitt WR, Arkadopoulos N, Kahaku E, Eguchi S, Khalili T, Arnaout W, Shackleton CR, Rozga J, Solomon B, Demetriou AA, Annu. Surg., 225, 484 (1997) 
Gerlach J, Trost T, Ryan CJ, Meibler M, Hole O, Muller C, Neuhaus P, Int. J. Artif. organs, 17, 549 (1994)
Hay PD, Veitch AR, Gaylor JD, Artif Organs, 25(2), 119 (2001) 
Gerlach JC, Mutig K, Sauer IM, Schrade P, Efimova E, Mieder T, Naumann G, Grunwald A, Pless G, Mas A, Bachmann S, Neuhaus P, Zeilinger K, Transplantation, 76(5), 781 (2003)
Mitaka T, Sato F, Mizuguchi T, Yokono T, Mochizuki Y, Hepatology, 29, 111 (1999) 
Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP, Science, 284(5417), 1168 (1999) 
Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M, Nature Medicine, 6, 1229 (2000) 
Michalopoulos GK, Defrances MC, Science, 276(5309), 60 (1997) 
Oh SH, Hatch HM, Petersen BE, Cell Developmental Biology, 13, 405 (2002) 
He ZP, Tan WQ, Tang YF, Zhang HJ, Feng MF, Cell Proliferation, 37, 177 (2004) 
Lowes KN, Croager EJ, Olynyk JK, Abraham LJ, Yeoh GC, J. Gastroenterology Hepatology, 18, 4 (2003) 
Sanchez A, Factor VM, Schroeder IS, Nagy P, Thorgeirsson SS, Hepatology, 39, 376 (2004) 
Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS, Hepatology, 31, 235 (2000) 
Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA, Nature, 406, 257 (2000) 
Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS, Hepatology, 32, 11 (2000) 
Newsome PN, Johanessen I, Boyle S, Dalakas E, McAulay KA, Samuel K, Rae F, Forrester L, Turner ML, Hayes PC, Harrison DJ, Bickmore WA, Plevris JN, Gastroenterology, 124, 1891 (2003) 
Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H, Stem Cells, 21, 217 (2003) 
Lee DH, Yoon HH, Lee JH, Lee KW, Lee SK, Kim SK, Choi JC, Kim YJ, Park JK, Biochem. Eng. J., in press (2004)