FEASIBILITY OF HEPATOCELLULAR TRANSPLANTATION VIA THE UMBILICAL VEIN IN PRENATAL AND PERINATAL LAMBS

Hepatocellular transplantation has previously been performed in experi mental animals by infusion of hepatocyte suspensions into the spleen o r portal venous system. Cells injected into these sites flow to the li ver and engraft within the hepatic parenchyma. We designed this study to evaluate the feasibility of hepatocellular transplantation through the umbilical vein in the prenatal or perinatal periods. Allogeneic sh eep hepatocytes were harvested, stained with the vital fluorescent dye DiI, and injected into the umbilical vein of fetal lambs at 85% gesta tion and term. Hemodynamic studies performed to assess the physiologic al impact of transplantation on the recipient animal demonstrated that the procedure was well tolerated. No significant short-term complicat ions were encountered and no lesions were found by conventional histol ogical examination at necropsy 1-17 days after transplantation. Engraf ted cells were identified within the liver by fluorescent microscopy a nd flow cytometry in 4/7 animals constituting 1.2-5% of the hepatocyte population. Fluorescent cellular material with the morphology of hepa tocytes, noncellular material, and fluorescent phagocytic cells were s een occasionally in other organs including lung, brain, adrenal, and p lacenta. These studies demonstrate the feasibility of performing hepat ocellular transplantation in the fetus via the umbilical vein in exper imental animals.