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Title: Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition
Authors: Aday, Sezin
Zoldan, Janet
Besnier, Marie
Carreto, Laura
Saif, Jaimy
Fernandes, Rui
Santos, Tiago
Bernardino, Liliana Inácio 
Langer, Robert 
Emanueli, Costanza
Ferreira, Lino 
Issue Date: 2017
Publisher: Nature
Project: We acknowledge the assistance of Dr. Glenn Paradis (MIT, MA, USA) for flow cytometry analyses of the microparticles and Dr. Thomas Kraehenbuehl for his scientific advice. This work was funded by FEDER (Fundo Europeu de Desenvolvimento Regional) through the Program COMPETE and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in the context of project PTDC/BIM-MED/1118/2012, and by the ERA Chair project ERA@UC (ref: 669088) through European Union´s Horizon 2020 program. S.A. acknowledges doctoral and postdoctoral grants from FCT (SFRH/BD/42871/2008 and SFRH/BPD/105172/2014). C.E. is a BHF Professor in Cardiovascular Science. This study was supported by awards from Leducq Foundation Transatlantic Network on vascular microRNAs, MIRVAD (13 CVD 02) and BHF Regenerative Medicine Centers (RM/13/2/30158). 
Serial title, monograph or event: Nature Communications
Volume: 8
Issue: 1
Abstract: Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652.
ISSN: 2041-1723
DOI: 10.1038/s41467-017-00746-7
Rights: openAccess
Appears in Collections:UC Bibliotecas - Artigos em Revistas Internacionais

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