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Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair

[Image: see text] Extracellular vesicles (EVs) are nanosized vesicles that carry cell-specific biomolecular information. Our previous studies showed that adult human bone marrow mesenchymal stem cell (BM-MSC)-derived EVs provide antiproteolytic and proregenerative effects in cultures of smooth muscl...

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Autores principales: S, Sajeesh, Camardo, Andrew, Dahal, Shataakshi, Ramamurthi, Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249416/
https://www.ncbi.nlm.nih.gov/pubmed/37093652
http://dx.doi.org/10.1021/acs.molpharmaceut.2c00769
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author S, Sajeesh
Camardo, Andrew
Dahal, Shataakshi
Ramamurthi, Anand
author_facet S, Sajeesh
Camardo, Andrew
Dahal, Shataakshi
Ramamurthi, Anand
author_sort S, Sajeesh
collection PubMed
description [Image: see text] Extracellular vesicles (EVs) are nanosized vesicles that carry cell-specific biomolecular information. Our previous studies showed that adult human bone marrow mesenchymal stem cell (BM-MSC)-derived EVs provide antiproteolytic and proregenerative effects in cultures of smooth muscle cells (SMCs) derived from an elastase-infused rat abdominal aortic aneurysm (AAA) model, and this is promising toward their use as a therapeutic platform for naturally irreversible elastic matrix aberrations in the aortic wall. Since systemically administered EVs poorly home into sites of tissue injury, disease strategies to improve their affinity toward target tissues are of great significance for EV-based treatment strategies. Toward this goal, in this work, we developed a postisolation surface modification strategy to target MSC-derived EVs to the AAA wall. The EVs were surface-conjugated with a short, synthetic, azide-modified peptide sequence for targeted binding to cathepsin K (CatK), a cysteine protease overexpressed in the AAA wall. Conjugation was performed using a copper-free click chemistry method. We determined that such conjugation improved EV uptake into cultured aneurysmal SMCs in culture and their binding to the wall of matrix injured vessels ex vivo. The proregenerative and antiproteolytic effects of MSC-EVs on cultured rat aneurysmal SMCs were also unaffected following peptide conjugation. From this study, it appears that modification with short synthetic peptide sequences seems to be an effective strategy for improving the cell-specific uptake of EVs and may be effective in facilitating AAA-targeted therapy.
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spelling pubmed-102494162023-06-09 Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair S, Sajeesh Camardo, Andrew Dahal, Shataakshi Ramamurthi, Anand Mol Pharm [Image: see text] Extracellular vesicles (EVs) are nanosized vesicles that carry cell-specific biomolecular information. Our previous studies showed that adult human bone marrow mesenchymal stem cell (BM-MSC)-derived EVs provide antiproteolytic and proregenerative effects in cultures of smooth muscle cells (SMCs) derived from an elastase-infused rat abdominal aortic aneurysm (AAA) model, and this is promising toward their use as a therapeutic platform for naturally irreversible elastic matrix aberrations in the aortic wall. Since systemically administered EVs poorly home into sites of tissue injury, disease strategies to improve their affinity toward target tissues are of great significance for EV-based treatment strategies. Toward this goal, in this work, we developed a postisolation surface modification strategy to target MSC-derived EVs to the AAA wall. The EVs were surface-conjugated with a short, synthetic, azide-modified peptide sequence for targeted binding to cathepsin K (CatK), a cysteine protease overexpressed in the AAA wall. Conjugation was performed using a copper-free click chemistry method. We determined that such conjugation improved EV uptake into cultured aneurysmal SMCs in culture and their binding to the wall of matrix injured vessels ex vivo. The proregenerative and antiproteolytic effects of MSC-EVs on cultured rat aneurysmal SMCs were also unaffected following peptide conjugation. From this study, it appears that modification with short synthetic peptide sequences seems to be an effective strategy for improving the cell-specific uptake of EVs and may be effective in facilitating AAA-targeted therapy. American Chemical Society 2023-04-24 /pmc/articles/PMC10249416/ /pubmed/37093652 http://dx.doi.org/10.1021/acs.molpharmaceut.2c00769 Text en © 2023 American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle S, Sajeesh
Camardo, Andrew
Dahal, Shataakshi
Ramamurthi, Anand
Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title_full Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title_fullStr Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title_full_unstemmed Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title_short Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair
title_sort surface-functionalized stem cell-derived extracellular vesicles for vascular elastic matrix regenerative repair
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249416/
https://www.ncbi.nlm.nih.gov/pubmed/37093652
http://dx.doi.org/10.1021/acs.molpharmaceut.2c00769
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