Abstract 10724: Intravenous Transfusion of iPS Cell-derived Vascular Progenitor Flk-1+ Cells Reduces Neointimal Formation After Vascular Injury
Background: Endothelial cell damage is an important early pathophysiological step of atherosclerosis and restenosis after angioplasty. Recently, it has been reported that vascular cells could be directionally induced from iPS cell-derived fetal liver kinase-1 positive (Flk-1+) cells. Here, we investigated the effect of intravenously transfused iPS cell-derived Flk-1+ cells on reendothelialization and neointima formation in a mouse model of vascular injury.
Methods and Results:Flk-1+ cells were induced from mouse iPS cells after 5 day of culture, and were purified by FACS sorting. Left femoral arteries of KSN nude mice were injured by steel wire inserted from the lumen. iPS cell-derived Flk-1+ or Flk-1- cells (1×106 cells) as a control were intravenously injected into mice at 24 h after the vascular injury. The deendothelialized areas were determined by Evans blue staining in a whole vessel preparation 7 days after vascular injury. At 21 days after vascular injury, delivery of iPS cell-derived Flk-1+ cells significantly attenuated intimal hyperplasia compared with that of control (p<0.01, n=8). Evans blue staining of the injured vessel revealed that administration of iPS cell-derived Flk-1+ cells was associated with a significant increase in reendothelialization compared with that of control (p<0.01, n=8). Furthermore, homing of PKH26-labeled iPS cell-derived Flk-1+ cells to the site of injury was detectable. In vitro experiments, the expression levels of CXCR4 in iPS cell-derived Flk-1+ cells were more than 25-fold higher than in iPS cell-derived Flk-1- cells. Stimulation of the ligand of CXCR4, SDF-1α enhanced migration and adhesion capacities in iPS cell-derived Flk-1+ cells, but not Flk-1- cells.
Conclusion: Intravenous transfusion of iPS cell-derived Flk-1+ cells home to the site of vascular injury, resulting in an enhanced reendothelialization associated with decreased neointimal formation. iPS cell-derived Flk-1+ cells could be a valuable source for the treatment of vascular dysfunction and prevention of restenosis after angioplasty.
- © 2012 by American Heart Association, Inc.