Rapid clearance of transplanted hepatocytes from pulmonary capillaries in rats indicates a wide safety margin of liver repopulation and the potentialof using surrogate albumin particles for safety analysis

Background/Aims: Applications of liver repopulation by hepatocyte transplan tation require analysis of cell biodistributions, particularly when portasy stemic shunting coexists. The aims of this study were to determine the fate of hepatocytes transplanted into the pulmonary vascular bed and to examine whether cell biodistributions could be approximated by convenient surrogat es. Methods: Rat hepatocytes and macroaggregated serum albumin particles of sim ilar sizes were injected into the portal and pulmonary vascular beds of rat s, followed by biodistribution, survival and function analyses. Results: Although functionally intact, virtually all hepatocytes were clear ed from the pulmonary capillaries within 24 h, Serum albumin levels increas ed minimally in Nagase analbuminemic rats with or without portacaval shunti ng to enhance delivery of portal factors to transplanted cells in lungs. De spite intravenous injection of hepatocytes approaching >1x10(9) cells in hu mans, the hemodynamic changes were limited to transient increases in right atrial pressures, The hepatocyte distributions in specific vascular beds we re largely reproduced by macroaggregated human serum albumin particles. Conclusions: Incidental intrapulmonary cell translocations during liver rep opulation will have a wide safety margin, Use of macroaggregated serum albu min particles as surrogates for initial short-term biodistribution and safe ty analysis will advance hepatocyte transplantation, as the cost of GLP-cer tified laboratories and consumption of scarce donor livers will be avoided.