THOUGHTS AND PROGRESS 941 zy back of the CF method is the removal of some por- tion of high density lipoprotein (HDL). But this side effect was mitigated by the larger pore size zyxwvu of the second filter, Evaflux-5A (10). The apheresis with anti-LDL antibodies (1 1) is more specific for LDL but ineffective for the removal of LP-X because the antibodies have an affinity zyxwvutsr to apolipoprotein B. Al- though antimitochondrial antibodies (AMA) are specific for PBC, we have not examined the changes in concentrations before and after different apheresis methods. It would be expected that AMA is partially removed by the CF method and not by the DSC method. Our experience in a patient with PBC suggests that the available methods for removal of LP-X are inadequate, and a more specific method without al- bumin substitution is desired for selective LP-X re- moval. References 1. Green PH. Lipoprotein metabolism in liver disease. La6 Res 2. Meredith JT. Lipoprotein-X. Arch Pathol Lab Med 1986; 3. Wally AK, Seidel D. Role of lipoprotein-)< in the pathogen- esis of cholestatic hypercholesterolemia. Uptake of lipopro- tein-X and its effect zyxwvutsr on 3-hydroxy-3-methylglutaryl coen- zyme A reductase and chylomicron remnant removal in human fibroblasts, lymphocytes and in the rat. J Clin Znvest 4. Turnberg LA, Mahoney MP, Gleeson MH, Freeman CB, Gowenlock AH. Plasmapheresis and plasma exchange in the treatment zyxwvutsrq of hyperlipaemia and xanthomatous neuropathy in patients with primary biliary cirrhosis. Gut 1972;13:976-81. zyxwvut 5. Yokoyama S, Hayashi R, Satani M, Yamamoto A. Specific removal of low-density lipoprotein (LDL) depression by plasmapheresis in familial hypercholesterolemia. Arterio- sclerosis 1985;5:613-22. 6. Tani N. Development of selective adsorbent and LDL aph- eresis system: Immobilized polyanions as LDL-specific ad- sorbent for LDL apheresis system. J Jpn Atherosclerosis Soc 1990;18:173-81. 7. Seidel D, Alaupovic P, Furman RH. A lipoprotein charac- terizing obstructive jaundice: I. Method for quantitative sep- aration and identification of lipoproteins in jaundiced sub- jects. J CIin Znvest 1969;48:1211-23. 8. Hashiguchi Y, Kawaguchi M, Nakanishi M, Matsumori Y, Kaneda Y, Nakai C, Mimura K, Matsuoka A. Simple, direct measurement of lipoprotein X in serum. Clin Chem 1982;28: 606-8. 9. Busnach G, Franceschini G, Chiesa G et al. Impaired effi- cacy of selective LDL-apheresis in primary biliary cirrhosis. Int J Artif Organs 1991;14:246-50. zyxwvutsr 10. Suehiro T, Sueoka A, Horiguchi J, Kojima S, Shiba M, Ya- mamoto A. Clinical evaluation of plasmapheresis using newly developed high performance EVAL secondary filter (Evaflux-SA) for hypercholesterolemia. Jpn J Artif Organs 11. Stoffel W, Demart T. Selective removal of apolipoprotein B-containing lipoproteins from blood plasma. Proc Natl Acad Sci USA 1981:78:611-5. Meth Biol Med 1983;7: 199-204. 110:1123-7. 1984;74:867-79. 1993;22:243-7. Reconstruction of Liver Tissue In Vitro: Geometry of Characteristic Flat Bed, Hollow Fiber, and Spouted Bed Bioreactors with Reference to the In Vivo Liver Augustinus Bader, "Erich Knop, Nils Fruhauf, Olaf Crome, fKlaus Boker, Uwe Christians, Marl Oldhafer, SBurkhard Ringe, $Rudolf Pichlmayr, and Karl-Friedrich Sewing at the Institut fur Allgemeine Pharmakologie, *Abt. fur Elektronenmikroskopie und Zellbiologie, TAbteilung fur Gastroenterologie und Hepatologie, and f Klinik fur Abdominal und Transplantationschirurgie, Medizinische Hochschule, Hannover, Germany Abstract: Bioreactors currently being developed for hy- brid artificial livers vary greatly with respect to their mi- croenvironment. The specific architecture modifies the relationship parenchymal and nonparenchymal cells have with the exchange surfaces of the bioreactor. Most de- signs are either based on hollow fiber, spouted bed, or flat bed devices. This diversity is contrasted by the uniform and unique organization of the in vivo liver. The liver cells are arranged as plates and both sinusoidal surfaces of the hepatocytes are enclosed within the matrix of the space of Disse. In this study we intended to define the in vivo liver tissue characteristics in a manner useful for an organotypical approach to hepatic tissue engineering. Transmission electron microscopy of an in vivo liver was utilized to describe these ratios. The ratios defined in this study are based on the constant hepatocellular expression of two sinusoidal surfaces. A relationship is established between the expression of the sinusoidal surfaces and their use as attachment and exchange surfaces inside a bioreactor. The presence of biliary surfaces and nonpa- renchymal cell surfaces is compared. The functional re- levance of an in vivo like extracellular matrix geometry for oxidative biotransformation of primary hepatocytes in vitro was studied using the two model drugs cyclosporin and rapamycin. The generation of the hydroxylated cy- closporin metabolites AM 9 and AM 1 and four rapamy- cin metabolites was analyzed by high performance liquid chromatography (HPLC). It is shown that the cell- specific biotransformation rates at 1 week in culture in matrix overlayed hepatocytes was 5-10 times that of he- patocytes without matrix overlay. Bilaminar membrane (BLM) bioreactors were used to reconstruct extracellular matrix geometry, three-dimensional cell plates, and sinu- soidal analogs in between cell plates. Key Words: Sand- wich culture-Ultrastructure-Cyclosporin-Rapa- mycin-Hepatocytes-Membranes-Oxygenation. Received September 1994; revised March 1995. Address correspondence and reprint requests to Dr. med. Augustinus Bader, Institut fiir Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, 30625 Hannover, Germany. Artif Organs, Vol. 19, No. 9, 1995