Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition

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.

Publication DOI: https://doi.org/10.1038/s41467-017-00746-7
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Cell Survival,Cell- and Tissue-Based Therapy,Cell-Derived Microparticles,Cyclin-Dependent Kinase Inhibitor p21/genetics,DNA-Binding Proteins/genetics,Endothelial Progenitor Cells/cytology,Fetal Blood/cytology,Gene Expression Regulation,Human Umbilical Vein Endothelial Cells,Humans,Ischemia/metabolism,MicroRNAs/metabolism,Neovascularization, Physiologic,Phosphorylation,Proto-Oncogene Proteins c-akt/metabolism,Vascular Endothelial Growth Factor A/metabolism,Vascular Endothelial Growth Factor Receptor-2/metabolism
Publication ISSN: 2041-1723
Full Text Link:
Related URLs: https://www.nat ... 467-017-00746-7 (Publisher URL)
PURE Output Type: Article
Published Date: 2017-09-29
Accepted Date: 2017-07-24
Authors: Aday, Sezin
Zoldan, Janet
Besnier, Marie
Carreto, Laura
Saif, Jaimy
Fernandes, Rui
Santos, Tiago
Bernardino, Liliana
Langer, Robert
Emanueli, Costanza
Ferreira, Lino

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