OBSERVATIONS ON INITIAL CELL LOSS AFTER INTRAPORTAL HEPATOCYTE TRANSPLANTATION OF 5'-BROMO-DEOXY-URIDINE-LABELED HEPATOCYTES

In the present study, attempts are made to improve posttransplant surv ival of intraportally transplanted hepatocytes in a syngeneic hepatocy te transplantation (HTX) model. Engrafted hepatocytes were detected an d quantified after pretransplant labeling with 5'-bromo-deoxy-uridine. In order to enhance the survival percentage, three mechanisms that po ssibly influence cell survival were manipulated: (1) administration of Matrigel(TM) (extracellular-matrix components, Matrigel Basement Memb rane Complex, Micronic BV, Lelystad, The Netherlands) in order to impr ove the environmental conditions of the transplanted hepatocytes; (2) immunosuppression of the recipients by 5 Gy total body irradiation and cyclosporin-A administration (25 mg/kg, 3 x weekly), and (3) Kupffer cell depletion by injection of dichloromethylene-diphosphonate-filled liposomes. The results were analyzed in relation to HTX without treatm ent. Cell survival was similar to 14% (10 days after HTX), and the tra nsplanted hepatocytes were distributed equally throughout the various recipient liver lobes. However, no increase was attained by Matrigel c oadministration, immunosuppression, or Kupffer cell depletion.