Therapeutic Reendothelialization by Induced Pluripotent Stem Cells After Vascular Injury—Brief Report

Objective— Endothelial damage is an early requisite step for atherosclerosis after vascular injury. It has been reported that vascular wall cells can develop from induced pluripotent stem (iPS) cell–derived fetal liver kinase-1–positive (Flk-1 + ) cells. Here, we investigated the efficacies of intravenously administered iPS cell–derived Flk-1 + cells on reendothelialization and neointimal hyperplasia in a mouse model of vascular injury. Approach and Results— Femoral arteries of KSN nude mice were injured using a steel wire. Mouse iPS cell–derived Flk-1 + or Flk-1 − cells were intravenously injected into those mice at 24 hours after vascular injury. Delivery of iPS cell–derived Flk-1 + cells significantly attenuated neointimal hyperplasia compared with controls. Evans blue staining of the injured vessel revealed that administration of iPS cell–derived Flk-1 + significantly enhanced reendothelialization compared with the Flk-1 − cell control group. Recruitment of PKH26-labeled iPS cell–derived Flk-1 + cells to the site of injury was also detectable. Expression level of CXCR4 in iPS cell–derived Flk-1 + cells was 7.5-fold higher than that of iPS cell–derived Flk-1 − cells. Stromal cell-derived factor-1α treatment significantly enhanced adhesion and migration of iPS cell–derived Flk-1 + cells to the endothelia, but these were not observed in Flk-1 − cells. Conclusions— Intravenously administered iPS cell–derived Flk-1 + cells are recruited to the site of vascular injury, thereby enhancing reendothelialization followed by suppression of neointimal hyperplasia. Administration of iPS cell–derived Flk-1 + cells is a potentially useful therapeutic means for vascular dysfunction and prevention of restenosis after angioplasty.