Effect of polylactic acid-O-carboxymethylated chitosan nanoparticles on immunological rejection in intraperitoneal porcine hepatocyte xenotransplantation of rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Previous research has proved good therapeutic effect on the acute hepatic failure by the treatment of polylactic acid-O-carboxymethylated chitosan(PLA-O-CMC) nanoparticles-cultured porcine hepatocytes embedded in type I collagen.OBJECTIVE:To investigate the effect of PLA-O-CMC nanoparticles on immunological rejection in intraperitoneal porcine hepatocyte xenotransplantation for treatment of acute liver failure rats.DESIGN,TIME AND SETTING:Randomized control animal experiments were carried out at the Institute of Hepatobiliary Surgery and Laboratory of Nerve Regeneration in Nantong University from May 2005 to May 2006.MATERIALSIn situ recirculating collagenase perfusion method was used to isolate porcine hepatocytes.64 SD rats were intraperitoneally injected with D-galactosamine to induce acute hepatic failure models.METHODS:Totally 64 rats were divided into four groupsModel group received no intervention;Nano-collagen hepatocytes group was transplanted with PLA-O-CMC nanoparticles-cultured porcine hepatocytes embedded in collagen gel,which was then wrapped up using greater omentum;Porcine hepatocytes embedded in collagen gel(collagen hepatocytes group) and free porcine hepatocytes suspension(pure hepatocytes group) were transplanted into peritoneal cavity of SD rats,respectively.At 48 hours following the modeling,the porcine hepatocytes transplantations were performed and the number of transplanted cells was 5.0?107 hepatocytes in all groups.MAIN OUTCOME MEASURES:The serum interleukin-2,interferon-?,IgG and IgM levels of rats were determined at days 1,2,3,5 and 7.The pathological changes of transplants were observed under microscope at days 1,3 and 7.RESULTS:There were no significant differences in serum interleukin-2 and interferon-? levels of all groups during 7 days post-transplantation.Serum IgG levels increased with a peak at day 3 after hepatocytes transplantation,and then began to decline.Serum IgG levels in nano-collagen hepatocytes group were lower than those in collagen hepatocytes group and pure hepatocytes group at days 2 and 3(P