Abstract
For the time being, the accomplishments of artificial organs have greatly alleviated the pains following inexorable functional degeneration or organ failure. In fact, the clinical practice of artificial organs outnumbers that of organ transplantation by 100 fold because of availability. However, a variety of critical issues and complications remain intractable in the development of artificial organs. Therefore, improvements/or breakthroughs in the existing technologies would be the key to exploring new therapeutic strategies and thereby upgrade the quality of treatments. In this thesis, two auxiliary techniques are proposed and attempted for the development of artificial kidney and bioartificial liver. One is the concept of an immunoadsorption wall that is address to the removal of beta-2-microglobulin; and the other is the application of centrifugal force to improve the immobilization efficiency of hepatocytes for a bioartificial liver reactor.To date, beta-2-microglobulin (B2M) accumulation and its clinical consequences remain one of the unsolved problems of renal replacement therapy. Removal during treatment by membranes permeable to B2M or whatever non-transplant techniques currently available is less than that accumulated between treatments. The concept of an immunoadsorption wall is a separation technique based on the combination of immunoisolation and immunoadsorption for removal of B2M. In this process, B2M molecules initially transport through immunoisolation barrier by diffusion, and then they are adsorbed onto the surface of a stationary phase that is formed by tightly packing the immunoadsorbent. The present investigations suggested that application of the concept to clinical use seems feasible and worthwhile. The concept, if validated, will help shape a novel multi-task type of artificial kidney based on the combination of different separation technologies.On the other hand, severe liver insufficiency, in particular a morbidity known as fulminant hepatitis, remains a highly lethal disease resistant to preservative treatment or blood purification therapies. It is now widely postulated that incorporation of the metabolic activities of intact, functioning hepatocytes are required to sustain patients* lives. A packed bed type of bioartificial liver using reticulated polyvinyl formal (PVF) resin as a substrate for hepatocyte attachment has been developed; however, the immobilization efficiency was estimated a low level of ca. 30 %. In this regard, a centrifugal cell immobilization (CCI) method based on the alternate action of centrifugal force and cell resuspension was attempted. The present study shows that higher efficiency (maximum ca. 75%), high density (107 cells/cm3-PVF), and relatively short period of immobilization time (ca. 15 min) can be attained by this newly developed method. Thus, it is concluded that the CCI method can provide an useful and effective means to immobilize cells within PVF cubes, which may overcome the major problem facing scaling up the packed-bed reactor system.