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

Sezin Aday, Janet Zoldan, Marie Besnier, Laura Carreto, Jaimy Saif, Rui Fernandes, Tiago Santos, Liliana Bernardino, Robert Langer, Costanza Emanueli () and Lino Ferreira ()
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Sezin Aday: University of Coimbra
Janet Zoldan: The University of Texas at Austin
Marie Besnier: University of Bristol
Laura Carreto: University of Aveiro
Jaimy Saif: University of Bristol
Rui Fernandes: Universidade do Porto
Tiago Santos: University of Beira Interior
Liliana Bernardino: University of Beira Interior
Robert Langer: Massachusetts Institute of Technology
Costanza Emanueli: University of Bristol
Lino Ferreira: University of Coimbra

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00746-7

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