Liver assist device employing transformed cell lines

Abstract

An improved extracorporeal liver assist device and method is provided which employs a blood perfusion membrane cultured with initially transformed hepatocytes until a confluent monolayer is developed, whereupon the hepatocytes are reverted to the somatic phenotype for perfusion purposes. Use of transformed hepatocytes permits serial subculturing to maintain a clinical supply of cells for the patient, while the in vitro proliferation characteristics and loss of contact inhibition of the transformed hepatocytes ensures rapid cell division and layer formation on the perfusion membranes. Virally transformed, temperature sensitive hepatocytes are preferred so that reversion of the cells can be accomplished by temperature change. The transformed hepatocytes may be cultured on the exterior surfaces of multiple capillary membrane cartridges, and subsequently reverted by elevating the temperature thereof. During perfusion, the patient's blood is passed through the lumen of the capillaries, and dissolved molecular species (e.g., bilirubin) diffuse through the membrane to be taken up and metabolized by the hepatocytes. Bathing solution is simultaneously passed around the exterior of the capillary tubes to remove metabolic wastes from the hepatocytes.

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