Hepatic artery vs. portal vein infusion of microbeads: a large animal pre-clinical model evaluating the intrahepatic capacity for cell infusion and imaging.
BACKGROUND
Islet xeno-transplantation via the portal vein has been proposed as an alternative of islet allo-transplantation for treatment of type 1 diabetes. However, the precise hepatic capacity has not been addressed.


METHODS
We mimicked cell transplantation by infusion of dogs with alginate/poly-1-lysine/alginate (APA) microbeads via either the portal vein (PV) or hepatic artery (HA). The maximal adaptable capacity for infused microbeads was evaluated by examination of vasculature, microvasculature, hepatic hemodynamics, portal vein, and hepatic artery pressures and liver function in the microbead recipient dogs.


RESULTS
PV but not HA dogs demonstrated elevated portal pressure during the infusion procedure in a dose-dependent manner. Four out of twelve PV dogs infused with 32,000 microbeads/kg developed acute liver infarction within 24 h after infusion with four of the remaining eight animals developing portal venous thrombosis within 24 h following infusion. All PV animals demonstrated abnormal alanine aminotransferase (ALT) values, and the extent and duration of increased ALT levels correlated with the increase in the number of microbeads infused. In contrast, HA animals infused with as many as 32,000 microbeads/kg had neither portal thrombosis nor abnormal liver function.


CONCLUSIONS
The capacity for intrahepatic cell infusion is finite and the intrahepatic artery may have a less hemodynamic interference impact on transplantation of cells into the liver when a larger volume of cells is required to achieve curable outcomes in both allo- and xeno-transplantation.
Wang
Wei
W
Cell Transplant and Gene Therapy Institute, The Third Xiang Ya Hospital of Central South University, Changsha, China.
Liu
Sheng
S
Zheng
Wei
W
Gao
Feng
F
Hawthorne
Wayne J
WJ
Yi
Shounan
S
D000410:Alanine Transaminase / Q000378:metabolism; D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004285:Dogs; D006439:Hemodynamics; D006499:Hepatic Artery / Q000502:physiology*; D006975:Hypertension, Portal / Q000139:chemically induced; D007262:Infusions, Intravenous / Q000009:adverse effects / Q000379:methods*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008863:Microspheres; D023421:Models, Animal; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D011169:Portal Vein / Q000502:physiology*; D013927:Thrombosis / Q000139:chemically induced; D014183:Transplantation, Heterologous / Q000379:methods
D000464:Alginates; D001672:Biocompatible Materials; C051546:alginate-polylysine-alginate; D011107:Polylysine; D000410:Alanine Transaminase