Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

Fleury, Audrey; Martinez, Maria Carmen; Lay, Soazig Le

doi:10.3389/fimmu.2014.00370

Cited by 107 publications

(83 citation statements)

References 86 publications

(108 reference statements)

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“…EVs, particularly exosomes, have attracted considerable interest for their potential use both as biomarkers and as vehicles for gene (or pseudogene) therapy . They are found in the circulation in healthy individuals, and their number rises in several CV conditions associated with inflammation; a growing number of reports have been documenting a role for them in endothelial function regulation .…”

Section: Therapeutic Potential Of Exosome/ Microvesicle‐contained Mirmentioning

confidence: 99%

Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?

Prattichizzo

Giuliani

Nigris

et al. 2016

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus (T2DM) is a major cause of cardiovascular (CV) disease. Several large clinical trials have shown that the risk for patients with diabetes of developing CV complications is only partially reduced by early, intensive glycaemic control and lifestyle interventions, and that such complications result from changes in complex, not fully explored networks that contribute to the maintenance of endothelial function. The accumulation of senescent cells and the low‐grade, systemic, inflammatory status that accompanies aging (inflammaging) are involved in the development of endothelial dysfunction. Such phenomena are modulated by epigenetic mechanisms, including microRNAs (miRNAs). MiRNAs can modulate virtually all gene transcripts. They can be secreted by living cells and taken up in active form by recipient cells, providing a new communication tool between tissues and organs. MiRNA deregulation has been associated with the development and progression of a number of age‐related diseases, including the enduring gene expression changes seen in patients with diabetes. We review recent evidence on miRNA changes in T2DM, focusing on the ability of diabetes‐associated miRNAs to modulate endothelial function, inflammaging and cellular senescence. We also discuss the hypothesis that miRNA‐containing extracellular vesicles (i.e. exosomes and microvesicles) could be harnessed to restore a ‘physiological’ signature capable of preventing or delaying the harmful systemic effects of T2DM.

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Section: Therapeutic Potential Of Exosome/ Microvesicle‐contained Mirmentioning

confidence: 99%

Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?

Prattichizzo

Giuliani

Nigris

et al. 2016

Diabetes Obesity Metabolism

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“…These results indicated that EPC-EVs fused with the cells and were degraded by the Golgi apparatus, releasing their cargo along the way. However, it was not possible to demonstrate an association between EPC-EVs and lysosomes, which have been suggested to digest EVs (29).…”

Section: Epc-derived Extracellular Vesicle Isolationmentioning

confidence: 84%

Endothelial progenitor cell-derived extracellular vesicle-meditated cell-to-cell communication regulates the proliferation and osteoblastic differentiation of bone mesenchymal stromal cells

Qin

Zhang

2017

Molecular Medicine Reports

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Bone tissue engineering is a promising treatment strategy to increase bone regeneration. Endothelial progenitor cells (EPCs) and bone marrow stromal cells (BMSCs) are commonly used to promote vessel formation and osteoblastic differentiation in tissue engineering. Previous studies have demonstrated that EPCs regulate both proliferation and differentiation of BMSCs. However, the underlying mechanism remains unclear. Understanding this mechanism is critical to developing more effective treatments. The role of extracellular vesicles in cell‑to‑cell communication has attracted substantial attention. These small vesicles deliver proteins, DNA, and RNA and consequently regulate the commitment, function, and differentiation of target cells. In the present study, EPC‑derived extracellular vesicles (EPC‑EVs were isolated using gradient ultracentrifugation and ultrafiltration and the influence of EPC‑EVs on BMSC osteoblastic differentiation and proliferation was examined in vitro. The results indicated that EPC‑EVs regulate the osteoblastic differentiation of BMSCs by inhibiting the expression of osteogenic genes and increasing proliferation in vitro. It is suggested that the results regarding the role of EPC‑EVs will provide a novel way to explain the crosstalk between EPCs and BMSCs.

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“…Exosome treatments have several advantages over the gene‐based therapies. Utilization of exosomes reduces immunogenicity and toxicity caused by biomaterial treatment, such as nanoparticles (Fleury et al, ). Qi et al reported that exosomes secreted from human induced pluripotent stem cell‐derived mesenchymal stem cells could accelerate critical‐sized bone defects healing by enhancing the proliferation and osteogenic differentiation of bone marrow MSCs derived from ovariectomized (OVX) rats (rBMSCs‐OVX) (Qi et al, ).…”

Section: Discussionmentioning

confidence: 99%

Exosomes secreted from mutant‐HIF‐1α‐modified bone‐marrow‐derived mesenchymal stem cells attenuate early steroid‐induced avascular necrosis of femoral head in rabbit

Li¹,

Liu²,

Li³

et al. 2017

Cell Biology International

100

111

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Mesenchymal stem cells (MSCs)-derived exosomes exhibit protective effects on damaged or diseased tissues. Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in bone development. However, HIF-1α is easily biodegradable under normoxic conditions. The bone-marrow-derived mesenchymal stem cells (BMSCs) were transfected with adenovirus carrying triple point-mutations (amino acids 402, 564, and 803) in the HIF-1α coding sequence (CDS). The mutant HIF-1α can efficiently express functional proteins under normoxic conditions. To date, no study has reported the role of exosomes secreted by mutant HIF-1α modified BMSCs in the recovery of the early steroid-induced avascular necrosis of femoral head (SANFH). In this study, we firstly analyzed exosomes derived from BMSCs modified by mutant (BMSC-Exos ) or wild-type HIF-1α (BMSC-Exos ). In vitro, we investigated the osteogenic differentiation capacity of BMSCs modified by BMSC-Exos or BMSC-Exos , and the angiogenesis effects of BMSC-Exos and BMSC-Exos on human umbilical vein endothelial cells (HUVECs). Besides, the healing of the femoral head was also assessed in vivo. We found that the potential of osteogenic differentiation of BMSCs treated with BMSC-Exos was higher than the wild-type group in vitro. In addition, BMSC-Exos stimulated the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Compared with the BMSC-Exos or PBS control group, the injection of BMSC-Exos into the necrosis region markedly accelerated the bone regeneration and angiogenesis, which were indicated by the increased trabecular reconstruction and microvascular density. Taken together, our data suggest that BMSC-Exos facilitates the repair of SANFH by enhancing osteogenesis and angiogenesis.

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Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

Cited by 107 publications

References 86 publications

Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?

Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?

Endothelial progenitor cell-derived extracellular vesicle-meditated cell-to-cell communication regulates the proliferation and osteoblastic differentiation of bone mesenchymal stromal cells

Exosomes secreted from mutant‐HIF‐1α‐modified bone‐marrow‐derived mesenchymal stem cells attenuate early steroid‐induced avascular necrosis of femoral head in rabbit

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