| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1985: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1984: ¥5,100,000 (Direct Cost: ¥5,100,000)
|
|---|
| Research Abstract |
Theoretical and experimental evaluations and the improvement of the performance of a hybrid-type artificial liver support system (ALSS) utilizing heterogeneous isolated hepatocytes were made from the engineering points of view.
Optimum conditions of the hepatocyte culture in terms of hepatocyte viability and metabolic functions, represented by metabolizing functions of a few solutes such as ammonia and caproic acid, were determined by batch culture experiments using isolated hepatocytes of the rats. Results of in vitro perfusion experiments were well correlated with the theoretically estimated performances based on the three compatments mass transfer model. Simulation studies demonstrates that the performance of ALSS is inevitably limited by the hepatocyte viability. Thus, the improvement of the performance of ALSS was also intended by employing the conditioned medium, and also by entrapping hepatocytes in calcium alginage hydrogel. With these modifications of culture conditions, the lower death rate constants <(k_v)> and about the same level of metabolic activity as in the suspension culture were obtained. In particular, entrapping of hepatocytes in bead-shaped or film-shaped calcium alginate gel resulted in a remarkable decrease in <k_v> by one to two order of magnitude smaller than that of suspension culture, while metabolic reaction rate constants remained almost unchanged.
A new ALSS module was constructed by use of 30 discs made of stainless steel mesh, which was coated by a thin film of hepatocytes containing hydrogel, 6 cm in diameter and 1 cm in annular width and mounted on a horizontally rotating axis. Extracorporeal purfusion experiments by means of this module on hepatic failure rabbits showed satisfactory metabolic performance of the module to eliminate ammonium in the rabbit blood. Thus, the ratating disc type artificial liver developed in the present project is expectable as a powerful candidate of future clinical use.
|
