Abstract
Background/Aims: Applications of liver repopulation by hepatocyte transplantation require analysis
of cell biodistributions, particularly when portasystemic 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 surrogates.
Methods: Rat hepatocytes and macroaggregated serum albumin particles of similar sizes were
injected into the portal and pulmonary vascular beds of rats, followed by biodistribution,
survival and function analyses.
Results: Although functionally intact, virtually all hepatocyteswere cleared from the pulmonary
capillaries within 24 h. Serum albumin levels increased minimally in Nagase analbuminemic
rats with or without portacaval shunting to enhance delivery of portal factors to
transplanted cells in lungs. Despite intravenous injection of hepatocytes approaching
>1×109 cells in humans, the hemodynamic changes were limited to transient increases in right
atrial pressures. The hepatocyte distributions in specific vascular beds were largely
reproduced by macroaggregated human serum albumin particles.
Conclusions: Incidental intrapulmonary cell translocations during liver repopulation will have
a wide safety margin. Use of macroaggregated serum albumin particles as surrogates
for initial short-term biodistribution and safety analysis will advance hepatocyte
transplantation, as the cost of GLP-certified laboratories and consumption of scarce
donor livers will be avoided.
Keywords
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Article info
Publication history
Accepted:
September 11,
1998
Received:
August 18,
1998
Identification
Copyright
© 1999 Published by Elsevier Inc.
