Transplantation of EPCs overexpressing PDGFR-β promotes vascular repair in the early phase after vascular injury.
Endothelial progenitor cells (EPCs) play important roles in the regeneration of the vascular endothelial cells (ECs). Platelet-derived growth factor receptor (PDGFR)-β is known to contribute to proliferation, migration, and angiogenesis of EPCs, this study aims to investigate effects of transplantation of EPCs overexpressing PDGFR-β on vascular regeneration.



We transplanted genetically modified EPCs overexpressing PDGFR-β into a mouse model with carotid artery injury. After 3 days of EPCs transplantation, the enhanced green fluorescent protein (EGFP)-expressing cells were found at the injury site and the lining of the lumen by laser scanning confocal microscope (LSCM). At 4, 7, and 14 days of the carotid artery injury, reendothelialization was evaluated by Evans Blue staining. Neointima formation was evaluated at day 14 with hematoxylin and eosin (HE) staining by calculating the neointimal area, medial area, and neointimal/media (NI/M) ratio. Intimal cell apoptosis was evaluated using TUNEL assay. Then we tested whether PDGF-BB-induced VSMC migration and PDGF-BB's function in reducing VSMC apoptosis can be attenuated by EPCs overexpressing PDGFR-β in a transwell co-culture system.



Our results showed that EPCs overexpressing PDGFR-β accelerates reendothelialization and mitigates neointimal formation at 14 days after injury. Moreover, we found that there is great possibility that EPCs overexpressing PDGFR-β enhanc VSMC apoptosis and suppress VSMC migration by competitive consumption of PDGF-BB in the early phase after carotid artery injury in mice.



We report the first in vivo and in vitro evidence that transplantation of genetically modified EPC can have a combined effect of both amplifying the reendothelialization capacity of EPCs and inhibiting neointima formation so as to facilitate better inhibition of adverse remodeling after vascular injury.
Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, China.
Hang
H
Wang
Intensive Care Unit, The sixth people's hospital of Chongqing, Nan'an District, Chongqing, 400060, China.
Yang-Guang
YG
Yin
Clinic center, Shenzhen Hornetcorn Biotechnology Company, Ltd, Shenzhen, 518400, China.
Hao
H
Huang
Institute of Cardiovascular Science, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Xiao-Hui
XH
Zhao
Institute of Cardiovascular Science, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Jie
J
Yu
Institute of Cardiovascular Science, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Qiang
Q
Wang
Institute of Cardiovascular Science, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Wei
W
Li
Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, China.
Ke-Yin
KY
Cai
Institute of Cardiovascular Science, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, China. dsfmd2015@163.com.
Shi-Fang
SF
Ding
D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000601:surgery*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058426:Neointima / Q000473:pathology; D012313:RNA / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D012038:Regeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods*
D012313:RNA; D020797:Receptor, Platelet-Derived Growth Factor beta
EPCs; Gene therapy; Neointima; PDGFR-β; Reendothelialization