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Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling
BACKGROUND: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263766/ https://www.ncbi.nlm.nih.gov/pubmed/35813344 http://dx.doi.org/10.21037/atm-21-4138 |
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author | Zhao, Ze-Liang Liu, Chao Wang, Qi-Zhang Wu, Hai-Wei Zheng, Jia-Wei |
author_facet | Zhao, Ze-Liang Liu, Chao Wang, Qi-Zhang Wu, Hai-Wei Zheng, Jia-Wei |
author_sort | Zhao, Ze-Liang |
collection | PubMed |
description | BACKGROUND: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear. METHODS: In this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs. RESULTS: E-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling. CONCLUSIONS: This study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future. |
format | Online Article Text |
id | pubmed-9263766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-92637662022-07-09 Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling Zhao, Ze-Liang Liu, Chao Wang, Qi-Zhang Wu, Hai-Wei Zheng, Jia-Wei Ann Transl Med Original Article BACKGROUND: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear. METHODS: In this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs. RESULTS: E-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling. CONCLUSIONS: This study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future. AME Publishing Company 2022-06 /pmc/articles/PMC9263766/ /pubmed/35813344 http://dx.doi.org/10.21037/atm-21-4138 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Zhao, Ze-Liang Liu, Chao Wang, Qi-Zhang Wu, Hai-Wei Zheng, Jia-Wei Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title | Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title_full | Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title_fullStr | Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title_full_unstemmed | Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title_short | Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling |
title_sort | engineered exosomes for targeted delivery of mir-187-3p suppress the viability of hemangioma stem cells by targeting notch signaling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263766/ https://www.ncbi.nlm.nih.gov/pubmed/35813344 http://dx.doi.org/10.21037/atm-21-4138 |
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