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{Aday:2021:10.1016/j.ymthe.2021.03.015,
author = {Aday, S and Hazan-Halevy, I and Chamorro-Jorganes, A and Anwar, M and Goldsmith, M and Beazley-Long, N and Sahoo, S and Dogra, N and Sweaad, W and Catapano, F and Ozaki-Tan, S and Angelini, GD and Madeddu, P and Benest, AV and Peer, D and Emanueli, C},
doi = {10.1016/j.ymthe.2021.03.015},
journal = {Molecular Therapy},
pages = {2239--2252},
title = {Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo},
url = {http://dx.doi.org/10.1016/j.ymthe.2021.03.015},
volume = {29},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.
AU  - Aday,S
AU  - Hazan-Halevy,I
AU  - Chamorro-Jorganes,A
AU  - Anwar,M
AU  - Goldsmith,M
AU  - Beazley-Long,N
AU  - Sahoo,S
AU  - Dogra,N
AU  - Sweaad,W
AU  - Catapano,F
AU  - Ozaki-Tan,S
AU  - Angelini,GD
AU  - Madeddu,P
AU  - Benest,AV
AU  - Peer,D
AU  - Emanueli,C
DO  - 10.1016/j.ymthe.2021.03.015
EP  - 2252
PY  - 2021///
SN  - 1525-0016
SP  - 2239
TI  - Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo
T2  - Molecular Therapy
UR  - http://dx.doi.org/10.1016/j.ymthe.2021.03.015
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33744469
UR  - https://www.sciencedirect.com/science/article/pii/S1525001621001441?via%3Dihub
UR  - http://hdl.handle.net/10044/1/88933
VL  - 29
ER  -
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