A Carrier-Mediated Transport of Toxins in a Hybrid Membrane. Safety Barrier between a Patients Blood and a Bioartificial Liver

Abstract

Combination of detoxifying liver support systems with liver cell bioreactors may have additional benefits for the treatment of liver failure due to the replacement of known and unknown metabolic activities of the liver. However, the problem of side effects and possible risks caused by the use of animal hepatocytes or hepatoma cells remains unsolved which underlines the need of a safety barrier between the patients blood and the extracorporeal bioreactor. Passive filters do not meet the requirements of such membranes, because in liver failure desired and undesired molecules in the patients blood share similar physicochemical properties. That challenges the development of biologically designed separation membranes. A hybrid membrane is formed by implementation of transport proteins into a highly permeable hollow fiber. The transport of free solutes and albumin bound toxins is tested in vitro in comparison with conventional high flux membranes. The transport characteristics for tightly albumin bound toxins are significantly improved for the hybrid membrane. The transport of albumin bound toxins across the membrane is not associated with albumin. The selectivity of the transport is evaluated in vivo. No significant loss of middle molecular weight hormones attached to other carrier proteins was observed. Neither transport of immunologically relevant proteins across the membrane nor loss of valuable proteins was measured. Also in vivo, a significant reduction of protein bound toxins and a transport of metabolically relevant solutes, like amino acids, was shown. The presented hybrid membrane may be used like an "intelligent membrane" as a safety barrier between the patients blood and cell devices.