Imperial College London
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Professor Costanza Emanueli

Faculty of Medicine, National Heart & Lung Institute

Chair in Cardiovascular Science
 
 
 
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Contact

 

c.emanueli Website

 
 
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Location

 

434ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Besnier:2018:10.1016/j.ymthe.2018.06.003,
author = {Besnier, M and Gasparino, S and Vono, R and Sangalli, E and Facoetti, A and Bollati, V and Cantone, L and Zaccagnini, G and Maimone, B and Fuschi, P and Da, Silva D and Schiavulli, M and Aday, S and Caputo, M and Madeddu, P and Emanueli, C and Martelli, F and Spinetti, G},
doi = {10.1016/j.ymthe.2018.06.003},
journal = {Molecular Therapy},
pages = {1694--1705},
title = {miR-210 enhances the therapeutic potential of bone-marrow-derived circulating proangiogenic cells in the setting of limb ischemia},
url = {http://dx.doi.org/10.1016/j.ymthe.2018.06.003},
volume = {26},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses. This study provides new mechanistic evidences for a role of miR-210 in PACs. PACs were obtained from either adult peripheral blood or cord blood. miR-210 expression was modulated with either an inhibitory complementary oligonucleotide (anti-miR-210) or a miRNA mimic (pre-miR-210). Scramble and absence of transfection served as controls. As expected, hypoxia increased miR-210 in PACs. In vivo, migration toward and adhesion to the ischemic endothelium facilitate the proangiogenic actions of transplanted PACs. In vitro, PAC migration toward SDF-1α/CXCL12 was impaired by anti-miR-210 and enhanced by pre-miR-210. Moreover, pre-miR-210 increased PAC adhesion to ECs and supported angiogenic responses in co-cultured ECs. These responses were not associated with changes in extracellular miR-210 and were abrogated by lentivirus-mediated EFNA3 overexpression. Finally, ex-vivo pre-miR-210 transfection predisposed PACs to induce post-ischemic therapeutic neovascularization and blood flow recovery in an immunodeficient mouse limb ischemia model. In conclusion, miR-210 modulates PAC functions and improves their therapeutic potential in limb ischemia.
AU  - Besnier,M
AU  - Gasparino,S
AU  - Vono,R
AU  - Sangalli,E
AU  - Facoetti,A
AU  - Bollati,V
AU  - Cantone,L
AU  - Zaccagnini,G
AU  - Maimone,B
AU  - Fuschi,P
AU  - Da,Silva D
AU  - Schiavulli,M
AU  - Aday,S
AU  - Caputo,M
AU  - Madeddu,P
AU  - Emanueli,C
AU  - Martelli,F
AU  - Spinetti,G
DO  - 10.1016/j.ymthe.2018.06.003
EP  - 1705
PY  - 2018///
SN  - 1525-0016
SP  - 1694
TI  - miR-210 enhances the therapeutic potential of bone-marrow-derived circulating proangiogenic cells in the setting of limb ischemia
T2  - Molecular Therapy
UR  - http://dx.doi.org/10.1016/j.ymthe.2018.06.003
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000439688600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/62067
VL  - 26
ER  -
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