HUMAN SERUM-ALBUMIN MICROSPHERES APPROXIMATE INITIAL ORGAN-SPECIFIC BIODISTRIBUTIONS OF TRANSPLANTED HEPATOCYTES AND ARE EFFECTIVE CELL SURROGATES FOR SAFETY STUDIES

Liver repopulation with transplanted hepatocytes will generate novel c ell-based therapies, although translocation of transplanted cells into lungs through portasystemic shunts has the potential for embolic comp lications, To facilitate safety analysis of hepatocyte transplantation , we wished to obtain effective cell surrogates and analyzed biodistri butions of similarly sized Tc-99m-labeled human serum albumin microsph eres and rat hepatocytes. Image analysis with dual (TC)-T-99m and In-1 11 labels indicated that cells and microspheres were similarly distrib uted in the Liver when injected into normal rats via the spleen. Also, their distributions were similar when injected via a femoral vein or the superior mesenteric vein with cells and microspheres localizing in lungs or liver, respectively. Upon intraportal injection in rats with portal hypertension, microspheres localized in both liver and lungs, consistent with portasystemic shunting. These data demonstrate that hu man serum albumin microspheres are effective cell surrogates for appro ximating the safety of hepatocyte transplantation and should be clinic ally useful, (C) 1998 Elsevier Science Inc.