Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 33, Issue 9, Pages 2218-2221Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.113.301313
Keywords
hyperplasia; induced pluripotent stem cells; vascular system injuries
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Funding
- Japan Science and Technology Agency [26-J-Jd08]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [20249045]
- Grants-in-Aid for Scientific Research [24659384, 20249045, 23390207, 23390208] Funding Source: KAKEN
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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-1 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.
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