Abstract
There have been many major advances in the field of liver transplantation in the past 30 yr. Orthotopic liver transplantation is currently the only established successful treatment for end-stage liver disease, with over 3000 liver transplantations being performed each year in more than 120 liver transplantation centers in the United States (1). There are several major challenges, however, that impede the widespread practice and applicability of organ transplantation. These include the critical shortage of donor organs, the high cost and technical difficulty of the procedures, and the intensive postoperative care involved, including those associated with life-long immunosuppression. Among these obstacles, the critical scarcity of donor organs, especially in the pediatric population, is perhaps the most significant. Each year, end-stage liver disease accounts for 26,000 deaths in the United States (2). Although the supply of donor organs has increased only slightly over the last 5 yr, the number of patients on the waiting list and the number of patients who die each year while on the waiting list have continued to grow at a disproportionate rate (1).
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References
1996 Annual Report of the U. S. Scientific Registry for Transplant Recipients and Organ Procurement and Transplantation Network—Transplant Data: 1988–1995. UNOS, Richmond, VA, and the Division of Transplantation, Bureau of Health Resources Development, Health Resources and Services Administration, U. S. Department of Health and Human Services, Rockville, MD.
American Liver Foundation (1996) Fact Sheet: Hepatitis, Liver and Gallbladder Diseases in the United States. Cedar Grove, NJ, American Liver Foundation.
Russell, P. S. (1985) Selective transplantation: an emerging concept. Ann. Surg. 201, 255–262.
Skalak, R. and Fox, C. F., eds. (1988) Tissue Engineering, Riss, New York.
Langer, R. and Vacanti, J. P. (1993) Tissue engineering. Science 260, 920–926.
Raper, S. E. and Wilson, J. M. (1993) Cell transplantation in liver-directed gene therapy. Cell Transplant. 2, 381–400.
Berry, M. N. and Friend, D. S. (1969) High yield preparation of isolated rat liver parenchymal cells. J. Cell Biol. 43, 506–520.
Seglen, P. O. (1976) Preparation of isolated rat liver cells. Methods Cell Biol. 13, 29–83.
Zhang, H., Miescher-Clemens, E., Drugas, G., Lee, S. M., and Colombani, P. (1992) J. Pediatr. Surg. 27, 312–316.
Ponder, K. P., Gupta, S., Leland, F., Darlington, G., Finegold, M., DeMayo, J., et al. (1991) Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation. Proc. Natl. Acad. Sci. USA 88, 1217–1221.
Gupta, S., Aragona, E., Vemuru, R. P., Bhargava, K. K., Burk, R. D., and Chowdhury, J. R. (1991) Permanent engraftment and function of hepatocytes delivered to the liver: implications for gene therapy and liver regeneration. Hepatology 14, 144–149.
Matas, A. J., Sutherland, D. E. R., Steffes, M. W., Mauer, S. M., Lowe, A., Simmons, R. L., and Najarian, J. S. (1976) Hepatocellular transplantation for metabolic deficiencies: decrease of plasma bilirubin in gunn rats. Science 192, 892–894.
Sutherland, D. E. R., Numata, M., Matas, A. J., Simmons, R. L., and Najarian, J. S. (1977) Hepatocellular transplantation in acute liver failure. Surgery 82, 124–132.
Sommer, B. G., Sutherland, D. E. R., Matas, A. J., Simmons, R. L., and Najarian, J. S. (1979) Hepatocellular transplantation for treatment of D-galactosamine-induced acute liver failure in rats. Transplantation Proc. 11, 578–584.
Holzman, M. D., Rozga, J., Neuzil, D. E, Griffin, D., Moscioni, A. D., and Demetriou, A. A. (1993) Selective intraportal hepatocyte transplantation in analbuminemic and gunn rats. Transplantation 55, 1213–1219.
Mito, M., Kusano, M., Onishi, T., Saito, T., and Ebata, H. (1978) Hepatocellular transplantation: morphological study on hepatocytes transplanted into rat spleen. Gastroenterol. Jpn. 13, 480–490.
Kusano, M. and Mito, M. (1982) Observations on the fine structure of long-survived isolated hepatocytes inoculated into rat spleen. Gastroenterology 82, 616–628.
Jiang, B., Sawa, M., Yamamoto, T., and Kasai, S. (1997) Enhancement of proliferation of intrasplenically transplanted hepatocytes in cirrhotic rats by hepatic stimulatory substance. Transplantation 63, 131–135.
Makowka, L., Rotstein, L. E., Falk, R. E., Falk, J. A., Zuk, R., Langer, B., Blendis, L. M., and Phillips, M. J. (1981) Allogeneic and xenogeneic hepatocyte transplantation. Transplantation Proc. 13, 855–859.
Vacanti, J. P., Morse, M. A., Saltzman, W. M., Domb, A. J., Perez-Atayde, A., and Langer, R. (1988) Selective cell transplantation using bioabsorbable artificial polymers as matrices. J. Pediatr. Surg. 23, 3–9.
Uyama, S., Kaufmann, P. M., Takeda, T., and Vacanti, J. P. (1993) Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation. Transplantation 55, 932–935.
Johnson, L. B., Aiken, J., Mooney, D., Schoo, B. L., GrifTith-Cima, L., Langer, R., and Vacanti, J. P. (1994) The mesentery as a laminated vascular bed for hepatocyte transplantation. Cell Transplantation 3, 273–281.
Selden, C, Gupta, S., Johnstone, R., and Hodgson, H. J. F. (1984) The pulmonary vascular bed as a site for implantation of isolated liver cells in inbred rats. Transplantation 38, 81–83.
Sandbichler, P., Then, P., Vogel, W., Erhart, R., Dietze, O., Philadelphy, H., et al. (1992) Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat. Gastroenterology 102, 605–609.
Jaffe, V, Darby, H., Selden, C, and Hodgson, H. J. F. (1988) The growth of transplanted liver cells within the pancreas. Transplantation 45, 497,498.
Vroemen, J. P. A. M., Buurman, W. A., van der Linden, C. J., Visser, R., Heirwegh, K. P. M., and Kootstra, G. (1988) Transplantation of isolated hepatocytes into the pancreas. Eur. Surg. Res. 20, 1–11.
Ricordi, C, Lacy, P. E., Callery, M. P., Park, P. W., and Flye, M. W. (1989) Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival. Surgery 105, 218–223.
Ricorde, C, Callery, M. P., Lacy, P. E., and Flye, M. W. (1989) Pancreatic islets enhance hepatocellular survival in combined hepatocyte-islet-cell transplantation. Transplantation Proc. 21, 2689–2690.
Jirtle, R. L., Biles, C, and Michalopoulos, G. (1980) Morphologic and histochemical analysis of hepatocytes transplanted into syngeneir hosts. Am. J. Pathol. 101, 115–126.
Jirtle, R. L. and Michalopoulos, G. (1982) Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res. 42, 3000–3004.
Takeda, T., Kim, T. H., Lee, S. K., Langer, R., and Vacanti, J. P. (1995) Hepatocyte transplantation in biodegradable polymer scaffolds using the dalmatian dog model of hyperuricosuria. Transplantation Proc. 27, 635–636.
Dixit, V, Darvasi, R., Arthur, M., Brezina, M., Lewin, K., and Gitnick, G. (1990) Restoration of liver function in gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. Hepatology 12, 1342–1349.
Dixit, V., Arthur, M., Reinhardt. R., and Gitnick, G. (1992) Improved function of microencapsulated hepatocytes in a hybrid bioartificial liver support system. Artif. Organs 16, 336–341.
Mooney, D. J., Kaufmann, P. M., Sano, K., McNamara, K. M., Vacanti, J. P., and Langer, R. (1994) Transplantation of hepatocytes using porous, biodegradable sponges. Transplantation Proc. 26, 3425–3436.
Mooney, D. J., Park, S., Kaufmann, P. M., Sano, K., McNamara, K., Vacanti, J. P., and Langer, R. (1995) Biodegradable sponges for hepatocyte transplantation. J. Biomed. Mater. Res. 29, 959–965.
Demetriou, A. A., Whiting, J. F., Feldman, D., Levenson, S. M., Chowdhury, N. R., Moscioni, A. D., Kram, M., and Chowdhury, J. R. (1986) Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes. Science 233, 1190–1192.
Demetriou, A. A., Whiting, J., Levenson, S. M., Chowdhury, N. R., Schechner, R., Michalski, S., Feldman, D., and Chowdhury, J. R. (1986) New method of hepatocyte transplantation and extracorporeal liver support. Ann. Surg. 204, 259–271.
Demetriou, A. A., Reisner, A., Sanchez, J., Levenson, S. M., Moscioni, A. D., and Chowdhury, J. R. (1988) Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats. Hepatology 8, 1006–1009.
Mooney, D., Hansen, L., Vacanti, J. P., Langer, R., Farmer, S., and Ingber, D. (1992) Switching from differentiation to growth in hepatocytes: control by extracellular matrix. J. Cell Physiol. 151, 497–504.
Asonuma K., Gilbert, J. C, Stein, J. E., Takeda, T., and Vacanti, J. P. (1992) Quantitation of transplanted hepatic mass necessary to cure the gunn rat model of hyperbilirubinemia. J. Pediatr. Surg. 27, 298–301.
Marchioro, T. L., Porter, K. A., Brown, B. I., Otte, J. B., and Starzl, T. E. (1967) The Effect of Partial Portacaval Transposition on the Canine Liver. Surgery 61, 723–732.
Starzl, T. E., Francavilla, A., Halgrimson, C. G., Francavilla, F. R., Porter, K. A., Brown, T. H., and Putnam, C. W. (1973) The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood. Surg. Gynecol. Obstet. 137, 179–199.
Sano, K., Cusick, R.A., Lee, H., Pollok, J. M., Kaufmann, P. M., Uyama, S., Mooney, D., Langer, R., and Vacanti, J. P. (1996) Regenerative signals for heterotopic hepatocyte transplantation. Transplantation Proc. 28, 1859,1860.
Kaufmann, P. M, Sano, K., Uyama, S., Takeda, T., and Vacanti, J. P. (1994) Heterotopic hepatocyte transplantation: assessing the impact of hepatotrophic stimulation. Transplantation Proc. 26, 2240,2241.
Nieto, J. A., Escandon, J., Betancor, C, Ramos, J., Canton, T., and Cuervas-Mons, V. (1989) Evidence that temporary complete occlusion of splenic vessels prevents massive embolization and sudden death associated with intrasplenic hepatocellular transplantation. Transplantation 47, 449,450.
Gupta, S, Vemuru, R. P., Lee, C. D., Yemeni, P. R., Aragona, E., and Burk, R. D. (1994) Hepatocytes exhibit superior transgene expression after transplantation into liver and spleen compared with peritoneal cavity or dorsal fat pad: implications for hepatic gene therapy. Hum. Gene Then 5, 959–967.
Rajvanshi, P., Kerr, A., Bhargava, K. K., Burk, R. D., and Gupta, S. (1996) Efficacy and safety of repeated hepatocyte transplantation for significant liver repopulation in rodents. Gastroenterology 111, 1092–1102.
Higgins, G. M. and Anderson, R. M. (1931) Experimental pathology of the liver: I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12, 186–202.
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Kim, S.S., Utsunomiya, H., Vacanti, J.P. (1999). Methods for the Implantation of Liver Cells. In: Morgan, J.R., Yarmush, M.L. (eds) Tissue Engineering Methods and Protocols. Methods in Molecular Medicine™, vol 18. Humana Press. https://doi.org/10.1385/0-89603-516-6:433
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DOI: https://doi.org/10.1385/0-89603-516-6:433
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