Imperial College London
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Professor David W. McComb

Faculty of Engineering, Department of Materials

Adjunct Professor
 
 
 
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Contact

 

+44 (0)20 7594 6750d.mccomb Website

 
 
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Location

 

Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rincon-Benavides:2023:10.1002/adtp.202200197,
author = {Rincon-Benavides, MA and Mendonca, NC and Cuellar-Gaviria, TZ and Salazar-Puerta, AI and Ortega-Pineda, L and Blackstone, BN and Deng, B and McComb, DW and Gallego-Perez, D and Powell, HM and Higuita-Castro, N},
doi = {10.1002/adtp.202200197},
journal = {Advanced Therapeutics},
title = {Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure},
url = {http://dx.doi.org/10.1002/adtp.202200197},
volume = {6},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Vasculogenic cell therapies have emerged as a powerful tool to increase vascularization and promote tissue repair/regeneration. Current approaches to cell therapies, however, rely mostly on progenitor cells, which pose significant risks (e.g., uncontrolled differentiation, tumorigenesis, and genetic/epigenetic abnormalities). Moreover, reprogramming methodologies used to generate induced endothelial cells (iECs) from induced pluripotent stem cells rely heavily on viral vectors, which pose additional translational limitations. This work describes the development of engineered human extracellular vesicles (EVs) capable of driving reprogramming-based vasculogenic therapies without the need for progenitor cells and/or viral vectors. EVs are derived from primary human dermal fibroblasts (HDFs), and are engineered to pack transcription factor genes/transcripts of ETV2, FLI1, and FOXC2 (EFF). In addition to EFF, the engineered EVs are also loaded with transcripts of angiogenic factors (e.g., VEGF-A, VEGF-KDR, FGF2). In vitro and in vivo studies indicate that such EVs effectively transfected HDFs and drive direct conversions towards iECs within 714 days. Finally, wound healing studies in mice indicate that engineered EVs lead to improved wound closure and vascularity. Altogether, these results show the potential of engineered human vasculogenic EVs to drive direct reprogramming processes of somatic cells towards iECs, and facilitate tissue repair/regeneration.
AU  - Rincon-Benavides,MA
AU  - Mendonca,NC
AU  - Cuellar-Gaviria,TZ
AU  - Salazar-Puerta,AI
AU  - Ortega-Pineda,L
AU  - Blackstone,BN
AU  - Deng,B
AU  - McComb,DW
AU  - Gallego-Perez,D
AU  - Powell,HM
AU  - Higuita-Castro,N
DO  - 10.1002/adtp.202200197
PY  - 2023///
TI  - Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure
T2  - Advanced Therapeutics
UR  - http://dx.doi.org/10.1002/adtp.202200197
VL  - 6
ER  -
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