Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition
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 solub...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/115214 https://orcid.org/0000-0003-4396-7812 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826212631312072704 |
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| author | Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Emanueli, Costanza Ferreira, Lino Aday, Sezin Langer, Robert S |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Emanueli, Costanza Ferreira, Lino Aday, Sezin Langer, Robert S |
| author_sort | Zoldan, Janet |
| collection | MIT |
| 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) - VEGF 165 , 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. |
| first_indexed | 2024-09-23T15:29:44Z |
| format | Article |
| id | mit-1721.1/115214 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:29:44Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1152142022-10-02T02:49:04Z Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Emanueli, Costanza Ferreira, Lino Aday, Sezin Langer, Robert S Massachusetts Institute of Technology. Department of Chemical Engineering Aday, Sezin Langer, Robert S 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) - VEGF 165 , 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. 2018-05-03T17:36:05Z 2018-05-03T17:36:05Z 2017-09 2016-11 2018-04-27T15:26:40Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/115214 Aday, Sezin et al. “Synthetic Microparticles Conjugated with VEGF165 Improve the Survival of Endothelial Progenitor Cells via microRNA-17 Inhibition.” Nature Communications 8, 1 (September 2017): 747 © 2017 The Author(s) https://orcid.org/0000-0003-4396-7812 https://orcid.org/0000-0003-4255-0492 http://dx.doi.org/10.1038/S41467-017-00746-7 Nature Communications Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Communications |
| spellingShingle | Zoldan, Janet Besnier, Marie Carreto, Laura Saif, Jaimy Fernandes, Rui Santos, Tiago Bernardino, Liliana Emanueli, Costanza Ferreira, Lino Aday, Sezin Langer, Robert S 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 |
| 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_short | 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 |
| url | http://hdl.handle.net/1721.1/115214 https://orcid.org/0000-0003-4396-7812 https://orcid.org/0000-0003-4255-0492 |
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