Therapeutic reendothelialization by induced pluripotent stem cells after vascular injury-brief report

Abstract

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. © 2013 American Heart Association, Inc.