Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction

Firoozi, Saman; Pahlavan, Sara; Ghanian, Mohammad Hossein; Rabbani, Shahram; Barekat, Maryam; Nazari, Abdoreza; Pakzad, Mohammad; Shekari, Faezeh; Hassani, Seyedeh‐Nafiseh; Moslem, Fariba; Lahrood, Fatemeh Nobakht; Soleimani, Mansoureh; Baharvand, Hossein

doi:10.1016/j.bbrc.2020.02.009

Cited by 40 publications

(22 citation statements)

References 23 publications

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“…BM-MSC exosomes engineered to contain the membrane Lamp2b fused to ischemic myocardium-targeting peptide were more efficiently internalized by hypoxic cardiomyocytes in vitro and showed enhanced accumulation in the post-MI heart in mice, resulting in improved effects in vivo including reduced myocardial inflammation, apoptosis, and fibrosis while improving vascularization and cardiac function [ 188 ]. Post-MI therapy by BM-MSC EVs was not improved using cell-free hydrogel formulations used to facilitate effectiveness of other cardiac therapies [ 189 ]. Aortic constriction in mice resulted in pressure overload-induced cardiac hypertrophy, myocardial apoptosis, and fibrosis that was attenuated by administration of mouse BM-MSC exosomes which, in vitro, prevented myocyte hypertrophy and apoptosis while promoting senescence of cardiac myofibroblasts [ 190 ].…”

Section: Cardiac Fibrosismentioning

confidence: 99%

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%

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

Brigstock

2021

Cells

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“…The umbilical cord blood derived MSCs were cultivated in MEM medium (Gibco, USA) containing 5 FBS (Gibco, USA) and 1 mM GlutaMAX (Gibco, USA). The EVs were isolated and identified as described previously [ 28 ]. Three tandem runs of centrifugation (2300 g for 20 min, 2300 g for 20 min, and 100000 g for 1 h, Optima L-100XP, USA) were conducted to centrifuge cells.…”

Section: Methodsmentioning

confidence: 99%

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

Chen

et al. 2021

Aging

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Background: The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported. Methods: Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound heating, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes. Results: Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR-497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs. Conclusions: We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.

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“…Like liver, kidney, and other organs, many methods can assist MSC-EVs in improving cardiac function and alleviating fibrosis, as shown in Table 2 . MSC-EVs are parcelled in PGN hydrogels [ 68 ], alginate hydrogels [ 69 ], and (RADA) 4 -SDKP hydrogels [ 70 ] to prolong retention so that EVs can be stably and sustainably released. The modification and preconditioning of EVs also can reduce cardiac fibrosis.…”

Section: Msc-evs and Fibrotic Diseasesmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases

Huang

Yang

2021

Stem Cell Res Ther

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Fibrosis is likely to occur in many tissues and organs to induce cicatrisation and dysfunction. The therapeutic regimens for delaying and even reversing fibrosis are quite limited at present. In nearly a decade, mesenchymal stem cells (MSCs) have been widely acknowledged as useful in treating fibrotic diseases in preclinical and clinical trials. Further preclinical studies indicated that the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are probably superior to that of MSCs. At present, MSC-EVs have attracted much attention in treating fibrosis of lung, liver, kidney, skin, and heart. By contrast, a significant knowledge-gap remains in treating fibrosis of other tissues and organs (including uterus, gastrointestinal tract, and peritoneum) with the aid of MSC-EVs. This review summarises the preclinical research status of MSC-EVs in treating fibrotic diseases and proposes solutions to existing problems, which contribute to further clinical research on the treatment of fibrotic diseases with MSC-EVs in the future.

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Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction

Cited by 40 publications

References 23 publications

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

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

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases

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