期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00746-7
关键词
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资金
- FEDER (Fundo Europeu de Desenvolvimento Regional) through COMPETE
- FCT (Fundacao para a Ciencia e a Tecnologia) [PTDC/BIM-MED/1118/2012]
- ERA Chair ERA@UC through European Union [669088]
- FCT [SFRH/BD/42871/2008, SFRH/BPD/105172/2014]
- BHF [SS/CH/15/1/31199]
- Leducq Foundation Transatlantic Network
- MIRVAD [13 CVD 02]
- BHF Regenerative Medicine Centers [RM/13/2/30158]
- British Heart Foundation [RG/15/5/31446] Funding Source: researchfish
- Fundação para a Ciência e a Tecnologia [PTDC/BIM-MED/1118/2012, SFRH/BPD/105172/2014, SFRH/BD/42871/2008] Funding Source: FCT
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.
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