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Intrasplenic hepatocyte transplantation: Evaluation of DNA synthesis and proliferation in auxiliary transplanted cells

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Research in Experimental Medicine

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.

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References

  1. 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

    PubMed  Google Scholar 

  2. 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

    PubMed  Google Scholar 

  3. Berry MN, Friend DS (1969) High yield preparation of isolated rat liver parenchymal cells. J Cell Biol 43:506–520

    PubMed  Google Scholar 

  4. Chirgwin JM, Przybyla AE, McDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonuclein acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299

    PubMed  Google Scholar 

  5. 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

    PubMed  Google Scholar 

  6. 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

    PubMed  Google Scholar 

  7. 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

    PubMed  Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. 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

    PubMed  Google Scholar 

  10. Flye MW, Lu X, Yu S (1987) Reversal of ischemic liver failure by intrasplenic liver cell transplantation. J Pediatric Surg 22/12:1212–1215

    Google Scholar 

  11. 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

    Google Scholar 

  12. 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

    Google Scholar 

  13. Jirtle RL, Michalopoulos G (1982) Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res 42:3000–3004

    PubMed  Google Scholar 

  14. Junge U, Creutzfeldt (1981) Trophic effect of portal blood in maintenance cultures of adult rat hepatocytes. Digestion 22:216–224

    PubMed  Google Scholar 

  15. Kusano M, Mito M (1982) Observations on the fine structure of long-survived isolated hepatocytes inoculated into rat spleen. Gastroenterology 82:616–628

    PubMed  Google Scholar 

  16. 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

    PubMed  Google Scholar 

  17. 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

    PubMed  Google Scholar 

  18. 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

    PubMed  Google Scholar 

  19. 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

    PubMed  Google Scholar 

  20. 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

    Google Scholar 

  21. 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

    PubMed  Google Scholar 

  22. 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

    PubMed  Google Scholar 

  23. 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

    PubMed  Google Scholar 

  24. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517

    PubMed  Google Scholar 

  25. Virolainen M (1963) Mitotic response in liver autograft after partial hepatectomy in the rat. Exp Cell Res 33:588–591

    Google Scholar 

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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

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  • DOI: https://doi.org/10.1007/BF01852262

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