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

Author

Listed:
  • Sezin Aday

    (University of Coimbra
    University of Coimbra
    Massachusetts Institute of Technology
    University of Bristol)

  • 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
    Imperial College of London)

  • Lino Ferreira

    (University of Coimbra
    University of Coimbra)

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.

Suggested Citation

  • Sezin Aday & Janet Zoldan & Marie Besnier & Laura Carreto & Jaimy Saif & Rui Fernandes & Tiago Santos & Liliana Bernardino & Robert Langer & Costanza Emanueli & Lino Ferreira, 2017. "Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00746-7
    DOI: 10.1038/s41467-017-00746-7
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