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Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction
BACKGROUND: Exosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201471/ https://www.ncbi.nlm.nih.gov/pubmed/30371236 http://dx.doi.org/10.1161/JAHA.118.008737 |
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author | Wang, Xu Chen, Yihuan Zhao, Zhenao Meng, Qingyou Yu, You Sun, Jiacheng Yang, Ziying Chen, Yueqiu Li, Jingjing Ma, Teng Liu, Hanghang Li, Zhen Yang, Junjie Shen, Zhenya |
author_facet | Wang, Xu Chen, Yihuan Zhao, Zhenao Meng, Qingyou Yu, You Sun, Jiacheng Yang, Ziying Chen, Yueqiu Li, Jingjing Ma, Teng Liu, Hanghang Li, Zhen Yang, Junjie Shen, Zhenya |
author_sort | Wang, Xu |
collection | PubMed |
description | BACKGROUND: Exosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium. METHODS AND RESULTS: We used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area. CONCLUSIONS: Our research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction. |
format | Online Article Text |
id | pubmed-6201471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62014712018-10-31 Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction Wang, Xu Chen, Yihuan Zhao, Zhenao Meng, Qingyou Yu, You Sun, Jiacheng Yang, Ziying Chen, Yueqiu Li, Jingjing Ma, Teng Liu, Hanghang Li, Zhen Yang, Junjie Shen, Zhenya J Am Heart Assoc Original Research BACKGROUND: Exosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium. METHODS AND RESULTS: We used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area. CONCLUSIONS: Our research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction. John Wiley and Sons Inc. 2018-07-27 /pmc/articles/PMC6201471/ /pubmed/30371236 http://dx.doi.org/10.1161/JAHA.118.008737 Text en © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Wang, Xu Chen, Yihuan Zhao, Zhenao Meng, Qingyou Yu, You Sun, Jiacheng Yang, Ziying Chen, Yueqiu Li, Jingjing Ma, Teng Liu, Hanghang Li, Zhen Yang, Junjie Shen, Zhenya Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title | Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title_full | Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title_fullStr | Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title_full_unstemmed | Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title_short | Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction |
title_sort | engineered exosomes with ischemic myocardium‐targeting peptide for targeted therapy in myocardial infarction |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201471/ https://www.ncbi.nlm.nih.gov/pubmed/30371236 http://dx.doi.org/10.1161/JAHA.118.008737 |
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