Transplantation of Human Adipose Tissue-Derived Multi-Lineage Progenitor Cells but not Adipose Tissue-Derived Stromal/Stem Cells Reduces Serum Cholesterol in Hyperlipidemic Watanabe Rabbits

摘要

Familial hypercholesterolemia (FH) is an autosomal codominant disease characterized by high concentrations of proatherogenic lipoproteins and premature atherosclerosis secondary to low-density lipoprotein (LDL) receptor deficiency. We have supposed that human adipose tissuederived multilineage progenitor cells (hADMPC, which were reported by Okura et al.) localized in the portal triad after transplantation via portal vein, subsequently integrated into the hepatic parenchyma and showed hepatocytic differentiation in vivo and lowered serum cholesterol in the WHHL rabbit, an animal model for homozygous FH. Here we showed that transplantation of hADMPC but not human adipose tissue-derived stromal/stem cells (hADSC, which were reported by Zuk et al.), could correct the metabolic defects of WHHL rabbit. Transplantation of hADMPC via portal vein resulted in significant reductions in total cholesterol, and the reductions maintained for 12 weeks. On the other hand, the total cholesterol levels of hADSC-transplanted group showed no significant difference to those of saline control group. To confirm transplantation of hADMPC but not hADSC reduces serum cholesterol in hyperlipidemic Watanabe rabbits, we examined LDL turnover studies using 125I-labelled LDL. 125I-LDL turnover study showed that the 24 hour clearance rate of LDL was significantly higher and LDL half-life was significantly shorter in the hADMPC transplanted-WHHL rabbits than those of saline control group. There was no significant difference on the 125I-LDL turnover study between hADSC-transplanted group and saline control one. These results indicated that ransplantation of hADMPC but not hADSC could correct the metabolic defect of the WHHL rabbit and be a novel therapy for inherited liver diseases.