THE MESENTERY AS A LAMINATED VASCULAR BED FOR HEPATOCYTE TRANSPLANTATION

The small bowel mesentery provides a unique structure of a large vascu larized surface area to support hepatocyte transplantation. Cell-seede d polymeric matrices can be juxtaposed in a relatively atraumatic mann er between leaves of mesentery such that adequate exchange of nutrient s and diffusion of gases can proceed in the interim while neovasculari zation occurs. Hepatocytes obtained from (RHA) Wistar rats by collagen ase perfusion were seeded onto nonwoven filamentous sheets of polyglyc olic acid 1 x 3 cm in size and 2 mm thickness to a density of 500,000 cells/cm(2). Twenty-six recipient Gunn rats (UDP-glucuronyl transferas e deficient) underwent laparotomy. Hepatocyte-ladened polymer sheets w ere placed between leaves of mesentery. Eight sheets were placed per a nimal and the leaves were approximated, treating a functional implant 1 x 3 x 2 cm. Biopsies between 5-99 days after implantation revealed n eovascularization, moderate inflammatory reaction and the presence of viable hepatocytes in 96% (25/26). Immunoperoxidase studies using anti -albumin antibody substantiated hepatocyte specific function in implan ts. HPLC profiles of bile from Gunn rats transplanted with hepatocytes from congeneic (RHA) rats demonstrated the presence of bilirubin conj ugates. There were no conjugation fractions seen in control gunn rats without hepatocyte transplantation. Although total serum bilirubin did not significantly decrease, conjugated bilirubin was identified in 46 % (12/26) animals after transplantation with congeneic hepatocytes. We conclude that the mesentery of the small bowel provides a large vascu larized surface for cell transplantation. Large numbers of metabolical ly active hepatocytes can engraft, vascularize, and show function. The mesentery may be a potential bed for clinical hepatocyte transplantat ion.