Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/92390 https://doi.org/10.1038/s41467-017-00746-7 |
Resumo: | 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. |
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Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibitionCell- and Tissue-Based TherapyCell-Derived MicroparticlesCyclin-Dependent Kinase Inhibitor p21DNA-Binding ProteinsEndothelial Progenitor CellsFetal BloodGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansIschemiaMicroRNAsNeovascularization, PhysiologicPhosphorylationProto-Oncogene Proteins c-aktVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Cell SurvivalSeveral 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.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).Nature2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/92390http://hdl.handle.net/10316/92390https://doi.org/10.1038/s41467-017-00746-7eng2041-1723Aday, SezinZoldan, JanetBesnier, MarieCarreto, LauraSaif, JaimyFernandes, RuiSantos, TiagoBernardino, Liliana InácioLanger, RobertEmanueli, CostanzaFerreira, Linoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-16T08:24:26Zoai:estudogeral.uc.pt:10316/92390Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:11:29.886599Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
title |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
spellingShingle |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition Aday, Sezin Cell- and Tissue-Based Therapy Cell-Derived Microparticles Cyclin-Dependent Kinase Inhibitor p21 DNA-Binding Proteins Endothelial Progenitor Cells Fetal Blood Gene Expression Regulation Human Umbilical Vein Endothelial Cells Humans Ischemia MicroRNAs Neovascularization, Physiologic Phosphorylation Proto-Oncogene Proteins c-akt Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Cell Survival |
title_short |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
title_full |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
title_fullStr |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
title_full_unstemmed |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
title_sort |
Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition |
author |
Aday, Sezin |
author_facet |
Aday, Sezin Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Inácio Langer, Robert Emanueli, Costanza Ferreira, Lino |
author_role |
author |
author2 |
Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Inácio Langer, Robert Emanueli, Costanza Ferreira, Lino |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Aday, Sezin Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Inácio Langer, Robert Emanueli, Costanza Ferreira, Lino |
dc.subject.por.fl_str_mv |
Cell- and Tissue-Based Therapy Cell-Derived Microparticles Cyclin-Dependent Kinase Inhibitor p21 DNA-Binding Proteins Endothelial Progenitor Cells Fetal Blood Gene Expression Regulation Human Umbilical Vein Endothelial Cells Humans Ischemia MicroRNAs Neovascularization, Physiologic Phosphorylation Proto-Oncogene Proteins c-akt Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Cell Survival |
topic |
Cell- and Tissue-Based Therapy Cell-Derived Microparticles Cyclin-Dependent Kinase Inhibitor p21 DNA-Binding Proteins Endothelial Progenitor Cells Fetal Blood Gene Expression Regulation Human Umbilical Vein Endothelial Cells Humans Ischemia MicroRNAs Neovascularization, Physiologic Phosphorylation Proto-Oncogene Proteins c-akt Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2 Cell Survival |
description |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/92390 http://hdl.handle.net/10316/92390 https://doi.org/10.1038/s41467-017-00746-7 |
url |
http://hdl.handle.net/10316/92390 https://doi.org/10.1038/s41467-017-00746-7 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Nature |
publisher.none.fl_str_mv |
Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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