Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization.
BACKGROUND
Hepatocyte transplantation could be an alternative to whole liver transplantation for the treatment of metabolic liver diseases. However, the results of clinical investigations suggest that the number of engrafted hepatocytes was insufficient to correct metabolic disorders. This may partly result from a lack of proliferation of transplanted hepatocytes. In rodents, portal ligation enhances hepatocyte engraftment after transplantation. We investigated the effects of partial portal ligation and embolization on engraftment and proliferation of transplanted hepatocytes in primates.


METHODS
Hepatocyte autotransplantation was performed in Macaca monkeys. The left lateral lobe was resected for hepatocyte isolation. The first group of monkeys underwent surgical ligation of the left and right anterior portal branches; in the second group, the same portal territories were obstructed by embolization with biological glue. To evaluate the proportion of cell engraftment hepatocytes were Hoechst-labeled and transplanted via the portal vein. Cell proliferation was measured by BrdU incorporation.


RESULTS
Hepatocyte proliferation was induced by both procedures but it was significantly higher after partial portal embolization (23.5% and 11.2% of dividing hepatocytes on days 3 and 7) than after ligation (3% and 0.8%). Hepatocytes engrafted more efficiently after embolization than after ligation. They proliferated and participated to liver regeneration representing 10% of the liver mass on day seven and their number remained constant on day 15.


CONCLUSIONS
These data suggest that partial portal embolization of the recipient liver improves engraftment of transplanted hepatocytes in a primate preclinical model providing a new strategy for hepatocyte transplantation.
Dagher
Ibrahim
I
Inserm U804 and University Paris XI, Kremlin-Bicêtre, France.
Boudechiche
Lyes
L
Branger
Julie
J
Coulomb-Lhermine
Aurore
A
Parouchev
Alexandre
A
Sentilhes
Loïc
L
Lin
Tao
T
Groyer-Picard
Marie-Thérèse
MT
Vons
Corinne
C
Hadchouel
Michelle
M
Pariente
Danièle
D
Andreoletti
Marion
M
Franco
Dominique
D
Weber
Anne
A
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D004621:Embolization, Therapeutic; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000628:therapy; D008115:Liver Regeneration; D008251:Macaca; D011169:Portal Vein / Q000473:pathology*; D011323:Primates; D016896:Treatment Outcome
D001973:Bromodeoxyuridine