MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair

Wang, Jinli; Lee, Christine J; Deci, Michael B.; Jasiewicz, Natalie; Verma, Anjali; Canty, John M.; Nguyen, Juliane

doi:10.1016/j.nano.2020.102201

Cited by 40 publications

(35 citation statements)

References 50 publications

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“…These EVs improved cardiac function and increased angiogenesis, and decreased inflammation and fibrosis in rats MI models and were enriched in miRs that were predicted to target PI3-AKT and mTOR [ 184 ]. Administration of miR-101a-enriched BM-MSC EVs in post-MI mice resulted in improved heart function and anti-inflammatory and anti-fibrotic effects and were due to EV-mediated polarization of macrophages to the anti-inflammatory phenotype, dampening of TGF-β expression, and inhibition of autophagy [ 185 ]. BM-MSC exosomes that contained elevated levels of HIF-1α promoted in vitro endothelial cell angiogenesis, migration, proliferation and expression of angiogenic factors while preserving cardiac function, promoting angiogenesis, and reducing fibrosis in a rat MI model [ 186 ].…”

Section: Cardiac Fibrosismentioning

confidence: 99%

“…While definitive answers to this question will likely require the use of genetically modified animals in which EV production, trafficking or responses are altered, support for intrinsic EV-mediated regulation of fibrosis has come from studies demonstrating fibrosis progression by injury-related EVs in vivo [ 68 , 72 , 109 , 170 , 179 , 182 , 251 , 257 , 258 , 259 , 260 ] and by the suppression of experimental renal or cardiac fibrosis in vivo by chemical- or drug-induced attenuation of EV secretion or miR content. [ 108 , 109 , 174 , 185 ]. A further mechanistic complication is that fibrosis is preceded by tissue injury and inflammation and the involvement of EVs in any one of these processes may be permissive for downstream pro-fibrotic pathways.…”

Section: Perspective and Concluding Remarksmentioning

confidence: 99%

“…In stz DN, EVs from BM-MSC were anti-fibrotic in the kidney but concomitantly induced autophagy and increased the expression of autophagy markers LC3 and beclin-1 while decreasing the expression of mTOR [ 126 ]. In cardiac MI models, EVs from iPSC-derived cardiomyocytes were anti-fibrotic and promoted myocardial repair and autophagy [ 219 ] but the reparative and anti-fibrotic affects EVs from BM-MSC were associated with decreased expression of LC3B, and EV therapy was enhanced by enrichment with miR-101 which blocks autophagy [ 185 ]. Although current data are not fully consistent as to the nature and direction of dynamic alterations of autophagy during fibrosing injury (which may reflect injury severity/type or cell-specific or temporal differences between the experimental systems), it is nonetheless evident that changes in autophagosome function and autophagic flux influence the production of EVs and their pathogenic payloads as well as providing a target for EV therapy.…”

Section: Perspective and Concluding Remarksmentioning

confidence: 99%

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Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

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Fibrosis is the unrelenting deposition of excessively large amounts of insoluble interstitial collagen due to profound matrigenic activities of wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It is a highly debilitating pathology that affects millions of people globally and leads to decreased function of vital organs and increased risk of cancer and end-stage organ disease. Extracellular vesicles (EVs) produced within the chronic wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many of the cell types involved in driving the fibrotic response. On the other hand, EVs from sources such as stem cells, uninjured parenchymal cells, and circulation have in vitro and in vivo anti-fibrotic activities that have provided novel and much-needed therapeutic options. Finally, EVs in body fluids of fibrotic individuals contain cargo components that may have utility as fibrosis biomarkers, which could circumvent current obstacles to fibrosis measurement in the clinic, allowing fibrosis stage, progression, or regression to be determined in a manner that is accurate, safe, minimally-invasive, and conducive to repetitive testing. This review highlights the rapid and recent progress in our understanding of EV-mediated fibrotic pathogenesis, anti-fibrotic therapy, and fibrosis staging in the lung, kidney, heart, liver, pancreas, and skin.

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Section: Cardiac Fibrosismentioning

confidence: 99%

Section: Perspective and Concluding Remarksmentioning

confidence: 99%

Section: Perspective and Concluding Remarksmentioning

confidence: 99%

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Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

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“…Several recent studies have implicated that MSC-exo could polarize macrophage to create an anti-inflammatory environment under myocardial I/R injury or MI [ 102 , 103 ]. MSC-exo, which transfers miR-182 and miR-101a into macrophage, has been demonstrated to reduce the number of M1 macrophages, polarize macrophages into M2 phenotype, and reduce infarct size and inflammatory response under myocardial I/R injury [ 102 , 104 ].…”

Section: Targeting the Therapeutic Role Of Macrophages Post-mimentioning

confidence: 99%

New Insights and Novel Therapeutic Potentials for Macrophages in Myocardial Infarction

et al. 2021

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Cardiovascular disease (CVD) has long been the leading cause of death worldwide, and myocardial infarction (MI) accounts for the greatest proportion of CVD. Recent research has revealed that inflammation plays a major role in the pathogenesis of CVD and other manifestations of atherosclerosis. Overwhelming evidence supports the view that macrophages, as the basic cell component of the innate immune system, play a pivotal role in atherosclerosis initiation and progression. Limited but indispensable resident macrophages have been detected in the healthy heart; however, the number of cardiac macrophages significantly increases during cardiac injury. In the early period of initial cardiac damage (e.g., MI), numerous classically activated macrophages (M1) originating from the bone marrow and spleen are rapidly recruited to damaged sites, where they are responsible for cardiac remodeling. After the inflammatory stage, the macrophages shift toward an alternatively activated phenotype (M2) that promotes cardiac repair. In addition, extensive studies have shown the therapeutic potential of macrophages as targets, especially for emerging nanoparticle-mediated drug delivery systems. In the present review, we focused on the role of macrophages in the development and progression of MI, factors regulating macrophage activation and function, and the therapeutic potential of macrophages in MI.

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“…Here, miR-101a was utilized for the inhibition of fibrosis, and the MSC exosomes were leveraged for the polarization of macrophages from M1 to M2. The therapeutic co-effects from the gene cargo and the carrier increased cardiac function in the MI model of mice [ 123 ]. Using ethanolamine (EA)-modified poly(glycidyl methacrylate) (PGEA) to fabricate heparin-cored nanoparticles (Hep@PGEA), Jing-Jun Nie et al sequentially delivered miR-499 and VEGF DNA for the inhibition of cardiomyocyte apoptosis in the early stages of MI and to promote angiogenesis at later stages.…”

Section: Modulating Different Cells For MI Treatmentmentioning

confidence: 99%

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Wang

Zhou

et al. 2021

Pharmaceutics

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Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.

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MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair

Cited by 40 publications

References 50 publications

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

New Insights and Novel Therapeutic Potentials for Macrophages in Myocardial Infarction

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

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