Summary
The value of isolated hepatocyte transplantation as a temporary support in acute hepatic failure remains controversial regarding the functional capacities of freshly isolated and transplanted hepatocytes. To evaluate the survival rate of intrasplenically transplanted liver cells and their response to a proliferation stimulus like partial hepatectomy,3H-thymidine incorporation into hepatic and auxiliary transplanted hepatocyte DNA was determined. The survival rate of intrasplenically transplanted hepatocytes was evaluated by analyses of m-albumin-RNA within the splenic tissue and compared to the morphological findings. The histological results show a marked decrease (> × 100) of intrasplenically transplanted hepatocytes within 1 week after injection. The amount of surviving cells then remained constant for 3 months without any signs of proliferation. After partial hepatectomy a stimulation of hepatic regeneration was observed in the remaining liver tissue but not in auxillary transplanted hepatocytes. M-albumin-RNA determination of auxiliary transplanted hepatocytes revealed a decrease of m-albumin-RNA concentration of > 100 times within 24 h after transplantation indicating early cell necrosis of the transplanted cells. Since intrasplenically transplanted hepatocytes underwent an early cell necrosis without any evidence for a directly postoperatively inducible cell proliferation, it is concluded that a sufficient metabolic support in acute hepatic failure cannot be taken into consideration.
Similar content being viewed by others
References
Baumgartner D, LaPlante-O'Neill PM, Sutherland DER, Najarian JS (1983) Effects of intrasplenic injection of hepatocytes, hepatocyte fragments and hepatocyte culture supernatants ond-galactosamine-induced liver failure in rats. Eur Surg Res 15:129–135
Berg RGM ten, Ernst P, Maldegem-Dronkers C van, Marquet R, Westbroek DL (1985) Effect of viable isolated hepatocytes or hepatocyte fractions on survival rate following galactosamine-induced acute liver failure. Eur Surg Res 17:109–118
Berry MN, Friend DS (1969) High yield preparation of isolated rat liver parenchymal cells. J Cell Biol 43:506–520
Chirgwin JM, Przybyla AE, McDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonuclein acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
Contini S, Pezzarossa A, Sansoni P, Mazzoni MP, Botta GC (1983) Hepatocellular transplantation in rats with toxic induced liver failure: results of iso-, allo- and xenografs. Ital J Surg Sci 13:25–30
Cuervas-Mons V, Cienfuegos JA, Rodriguez V, Eroles G, Pinedo I, Santamaria L, Ramos J, Ortiz JL, Castillo-Olivares JL, Segovia JM (1985) Long-term evaluation of isolated syngeneic hepatocytes transplanted into the normal rat spleen by Tc-99M-HIDA scintigraphy. Transplantation 39:87–90
Darby H, Gupta S, Johnstone R, Selden C, Hodgson HJ (1986) Observations on rat spleen reticulum during the development of syngeneic hepatocellular implants. Br J Exp Pathol 67:329–339
Demma I, Houssin D, Capron M, Minato M, Morin J, Gigou M, Szekely AM, Bismuth H (1986) Therapeutic efficacy of the transplantation of isolated hepatocytes in rats with surgically induced acute hepatic failure: A study of the mechanism. Eur Surg Res 18:12–18
Ebata H, Kusano M, Onishi T, Saito T, Mito M (1978) Liver regeneration utilizing isolated hepatocytes transplanted into the rat spleen. Surg Forum 29:338–340
Flye MW, Lu X, Yu S (1987) Reversal of ischemic liver failure by intrasplenic liver cell transplantation. J Pediatric Surg 22/12:1212–1215
Grundmann R, Koebe HG, Waters W (1986) Transplantation of cryopreserved hepatocytes or liver cytosol injection in the treatment of acute liver failure in rats. Res Exp Med 186:141–149
Higgins GM, Anderson RM (1931) Experimental pathology of the liver I: Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202
Jirtle RL, Michalopoulos G (1982) Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res 42:3000–3004
Junge U, Creutzfeldt (1981) Trophic effect of portal blood in maintenance cultures of adult rat hepatocytes. Digestion 22:216–224
Kusano M, Mito M (1982) Observations on the fine structure of long-survived isolated hepatocytes inoculated into rat spleen. Gastroenterology 82:616–628
LaBreque DR (1979) The role of hepatotrophic factors in liver regeneration — a brief review including a preliminary report of the in vitro effects of hepatic regenerative stimulator substance (SS). Yale J Biol Med 52:49–60
Makowka L, Falk RE, Rotstein LE, Falk JA, Nossal N, Langer B, Blendis LM, Phillips MJ (1980) Reversal of experimental acute hepatic failure in the rat. J Surg Res 29:479–487
Makowka L, Rotstein LE, Falk RE, Falk JA, Zuk R, Langer B, Blendis LM, Phillips MJ (1981) Studies into the mechanism of reversal of experimental acute hepatic failure by hepatocyte transplantation. Can J Surg 24:39–44
Makowka L, Falk RE, Falk JA, Teodorczyk-Injeyan J, Venturi D, Rotstein LE, Falk W, Langer B, Blendis LM, Phillips MJ (1983) The effect of liver cytosol on hepatic regeneration and tumor growth. Cancer 51:2181–2190
Minato M, Houssin D, Demma I, Morin J, Gigou M, Szekely AM, Bismuth H (1984) Transplantation of hepatocytes for treatment of surgically-induced acute hepatic failure in the rat. Eur Surg Res 16:162–169
Mito M, Kusano M, Onishi T, Saito T, Ebata H (1978) Hepatocellular transplantation — Morphological study on hepatocytes transplanted into rat spleen. Gastroenterol Jpn 13:480–490
Mito M, Ebata H, Kusano M, Onishi T, Saito T, Sakamoto S (1979) Morphology and function of isolated hepatocytes transplanted into rat spleen. Transplantation 28:499–505
Sommer BG, Sutherland DER, Matas AJ, Simmons RL, Najarian JS (1979) Hepatocellular transplantation for treatment ofd-galactosamine-induced acute liver failure in rats. Transplant Proc 11:578–584
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Virolainen M (1963) Mitotic response in liver autograft after partial hepatectomy in the rat. Exp Cell Res 33:588–591
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Henne-Bruns, D., Ambrass, F.O., Schmiegelow, P. et al. Intrasplenic hepatocyte transplantation: Evaluation of DNA synthesis and proliferation in auxiliary transplanted cells. Res. Exp. Med. 189, 295–302 (1989). https://doi.org/10.1007/BF01852262
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01852262