Abstract 9197: In Situ Stem Cell Therapy Using Human Adipose Tissue-Derived Multi-lineage Progenitor Cells Combined with HMG-CoA Reductase Inhibitor Synergistically Reduce Serum Cholesterol Level in Hyperlipidemic Watanabe Rabbits

Abstract

Background : Familial hypercholesterolemia (FH) is an autosomal co-dominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis. We examined the response to the combination of in situ stem cell therapy using human adipose tissue-derived multi-lineage progenitor stem cells (hADMPC) and HMG-CoA reductase inhibitor in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of homozygous FH. Methods : WHHL rabbits received hADMPC via the portal vein, followed by a course of immunosuppressive therapy to avoid xenogenic rejection. In situ reprogramming of the hADMPC into hepatocytes was examined by immunohistochemistry and QT-PCR analysis. Lipid profiles were examined before-transplantation, after-transplantation and/or after transplantation followed by 4 weeks of treatment with HMG-CoA reductase inhibitor, pravastatin. LDL clearance was examined at the end of the study by125I-LDL turnover studies. Results : The hADMPC were integrated into the hepatic parenchyma after transplantation, and expressed human hepatocyte markers such as albumin, indicating that these cells were reprogrammed into hepatocytes-like cells in situ . hADMPC-transplantation reduced serum cholesterol levels and improved LDL turnover. Transplantation followed by 4-week treatment with pravastatin further reduced serum cholesterol levels compared with untreated rabbits. LDL clearance was significantly augmented in the pravastatin-treated rabbits. Conclusion : Transplantation of hADMPC corrected the metabolic defects and the effects were augmented by statins in WHHL rabbits, in which no significant effects were observed by statins. In situ stem cell therapy combined with other drugs is a potentially useful strategy for FH.