Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide
| Autor: | Ke Huang, Adam C. Vandergriff, Li Qian, Michael Taylor Hensley, Shiqi Hu, Ke Cheng, Deliang Shen, Thomas G. Caranasos |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Angiogenesis Myocardial Infarction Ischemia Medicine (miscellaneous) exosomes heart disease Pharmacology Exosome 03 medical and health sciences Fibrosis Animals Medicine Myocytes Cardiac Molecular Targeted Therapy Pharmacology Toxicology and Pharmaceutics (miscellaneous) Targeting Biological Products business.industry cardiac regeneration medicine.disease Microvesicles In vitro Rats Biological Therapy Disease Models Animal Treatment Outcome 030104 developmental biology Echocardiography Administration Intravenous Peptides business Reperfusion injury Ex vivo Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.20524 |
| Popis: | Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct. Though effective in a research setting, this method is not clinically appealing due to its invasive nature. We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart. Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker. Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy. In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells. For the animal study, we utilized an ischemia/reperfusion rat model. Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery. Echocardiography was performed 4 h after surgery and 21 d after surgery. At 21 d, animals were sacrificed, and organs were collected for analysis. Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes. In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs. Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes. Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction. By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis. |
| Databáze: | OpenAIRE |
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