Abstract 9201: Transplantation of Adipose Tissue-Derived Multi-Lineage Progenitor Cells Reduces Serum Cholesterol in Hyperlipidemic Watanabe Rabbits
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 in situ stem cell therapy using adipose tissue-derived multi-lineage progenitor stem cells (hADMPC) in the LDL-receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH.
Methods: WHHL rabbits received either normal control rabbit-derived, GFP-rabbit-derived or WHHL rabbit-derived ADMPC (normal-ADMPC, GFP-ADMPC and diseased-ADMPC, respectively) via the portal vein. This was followed by 12-week immunosuppressive therapy to avoid allogenic rejection. In situ survival and differentiation of the ADMPC into hepatocytes was examined by flow cytometry and immunohistochemical analysis, respectively. Lipid profile was examined before-, and 4-, 8- and 12 weeks after transplantation. LDL clearance was examined at the end of the study by125I-LDL turnover.
Results: In situ survival of GFP-ADMPC was confirmed after transplantation. The cells integrated into the hepatic parenchyma and co-expressed GFP and hepatocyte markers such as albumin, indicating that the cells were reprogrammed into hepatocytes-like cells in situ. Transplantation of normal-ADMPC but not diseased-ADMPC resulted in a significant reduction of serum total- and LDL- cholesterol after transplantation. 125I-LDL turnover study showed significant improvement in the rate of LDL clearance in the WHHL rabbits with transplanted normal-ADMPC but not in those transplanted with diseased-ADMPC.
Conclusion: Transplantation of ADMPC but not diseased ones corrected the metabolic defects in WHHL rabbits, suggesting that ADMPC transplantation is a potentially useful therapy for FH.
- © 2011 by American Heart Association, Inc.