LONG-TERM CORRECTION OF ALBUMIN LEVELS IN THE NAGASE ANALBUMINEMIC RAT - REPOPULATION OF THE LIVER BY TRANSPLANTED NORMAL HEPATOCYTES UNDERA REGENERATION RESPONSE

Numerous studies have reported successful transplantation of hepatocyt es with demonstration of function, However, none have shown long-term correction of a liver-related metabolic defect, Male Nagase analbumine mic rats, immunosuppressed with cyclosporin-A, were transplanted with normal hepatocytes (2 x 10(7) cells/rat) isolated from allogeneic male Sprague-Dawley rat donors. Hepatocytes were selectively transplanted via the portal vein tributary into the posterior liver lobes of Nagase analbuminemic rats, Following 2 wk, to allow engraftment, selected tr ansplanted rats (Group I) were reoperated and the portal venous branch supplying the anterior liver lobes was permanently ligated, resulting in their atrophy and induction of regeneration in the residual transp lant-bearing lobes, Control fats consisted of: Group II-transplanted w ith normal hepatocytes without portal branch ligation; Group III-trans planted with analbuminemic hepatocytes with portal branch ligation; an d Group IV-nontransplanted analbuminemic rats with portal branch ligat ion, The experimental period extended to 3 mo posttransplantation, All rats transplanted with normal hepatocytes demonstrated a significant elevation in serum albumin levels (ELISA). Group I rats had dramatic e levations in serum albumin to near normal levels (1.78 +/- 0.20 g/dl), and maintained these levels until the end of the experiment, Albumin levels in Group II rats reached 0.26 +/- 0.07 g/dl (p < 0.001), wherea s Group III and IV rats showed no changes in serum albumin levels thro ughout the experiment, Immunohistology of liver tissue obtained from G roup I rats, demonstrated Large numbers (22.6 +/- 7.5%) of albumin-pos itive hepatocytes populating the recipient liver. This is the first re port of near-total and sustained correction of a genetic defect in liv er function in an experimental animal model following allogeneic hepat ocyte transplantation.