Liver assist device employing transformed cell lines

Details Liver assist device employing transformed cell lines Liver assist device employing transformed cell lines

1986-11-17

1989-08-01

Warden, Robert J.

Chemistry: molecular biology and microbiology

Maintaining blood or sperm in a physiologically active state...

435235, 4352401, 435240241, 435283, 435284, A01N 102, C12N 700, C12N 500

Patent

active

048533246

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.

REFERENCES:
patent: 3489647 (1970-01-01), Kolobow
patent: 4242459 (1980-12-01), Chick et al.
Establishment of a Fetal Rat Liver Cell Line that Retains Differentiated Liver Functions; Susanna E. Schlegel-Haueter, Werner Schlegel & Janice Y. Chou; May 1980.
Temperature-Sensitive Fetal Liver Cells; A Model for Hepatocellular Differentiation; Janice Yang Chou & Fumiyuki Ito; 1983.
Study of Liver Differentiation in Vitrol, Janice Yang Chou & Susanna E. Schlegel-Haueter; May 1981.
Cell Types in Long-Term Propagable Cultures of Rat Liver; J. W. Girsham; 1980.
Chou et al, Chemical Abstracts, 100:136285n (1984).
Knazek et al., Science, vol. 178, pp. 65-67 (Oct. 6, 1972).

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