Cardiovascular progenitor–derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure

Kervadec, Anaïs; Bellamy, Valérie; Harane, Nadia El; Arakélian, Lousineh; Vanneaux, Valérie; Cacciapuoti, Isabelle; Nemetalla, Hany; Perier, Marie Cécile; Toeg, Hadi; Richart, Adèle; Lemitre, Mathilde; Yin, Min; Loyer, Xavier; Larghero, Jérôme; Hagège, Albert; Ruel, Marc; Boulanger, Chantal M.; Silvestre, Jean‐Sébastien; Menasché, Philippe; Renault, Nicolas

doi:10.1016/j.healun.2016.01.013

Cited by 176 publications

(127 citation statements)

References 35 publications

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“…A recent study showed that human CPCs derived extracellular vesicles reproduced the similar beneficial effects compared to their parent cell in chronic heart failure model 18 . While interesting, this study looked at embryonic stem cell-derived CPCs and not isolated from tissue.…”

Section: Discussionmentioning

confidence: 91%

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients

Agarwal

George

Bhutani

et al. 2017

Circulation Research

145

153

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Rationale Studies have demonstrated that exosomes can repair cardiac tissue post myocardial infarction (MI) and recapitulate the benefits of cellular therapy. Objective We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes, in a rat model of ischemia reperfusion (IR) injury. Methods and Results Human CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions. Exosomes were isolated from the culture-conditioned media and delivered to athymic rats following IR injury. Echocardiography at day-3 post-MI suggested statistically improved function in neonatal hypoxic and neonatal normoxic groups compared to saline-treated controls. At 28 days post-MI exosomes derived from neonatal normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly improved cardiac function compared to saline-treated controls. Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups compared to controls. Finally, using sequencing data, a computational model was generated to link microRNA levels to specific outcomes. Conclusion CPC exosomes derived from neonates improved cardiac function independent of culture oxygen levels, while CPC-exosomes from older children were not reparative unless subjected to hypoxic conditions. Cardiac functional improvements were associated with increased angiogenesis, reduced fibrosis and improved hypertrophy resulting in improved cardiac function; however, mechanisms for normoxic neonatal CPC exosomes improved function independent of those mechanisms. This is the first study of its kind demonstrating that donor age and oxygen content in the microenvironment significantly alter the efficacy of human CPC-derived exosomes.

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Section: Discussionmentioning

confidence: 91%

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients

Agarwal

George

Bhutani

et al. 2017

Circulation Research

145

153

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“…Hypoxia stimulated exosome release from CPCs and modified their molecular content, as discussed below. Kervadec et al (35) showed that CPC-derived EVs recapitulated the beneficial effects of their parent cells in chronic heart failure models.…”

Section: Visualization Of Exosome Release From Cpcsmentioning

confidence: 99%

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Barile¹,

Milano²,

Vassalli³

2017

Stem Cell Investig.

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When injected into acutely infarcted rodent or pig hearts, naturally secreted nanovesicles known as exosomes from cardiac-derived progenitor cells (CPCs) reduce scar size and improve cardiac function. In this regard, exosomes fully mimic the benefits of injecting their parent cells. This recognition paves the way to the development of exosome-based, cell-free treatments for heart disease that could possibly supplant cellbased therapies. Mechanisms of benefit of these vesicles are incompletely understood but cytoprotection, stimulation of angiogenesis, induction of antifibrotic cardiac fibroblasts, and modulation of M1/M2 polarization of macrophages infiltrating the infarcted region can all play important roles. Accordingly, the beneficial molecules carried by CPC-secreted exosomes have been identified only in part but cytoprotective and proangiogenic microRNAs (miRNA) and proteins have been described. Besides CPC-secreted exosomes, vesicles released from other cell types including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iSPCs) have also been associated with cardioprotection. This review aims to discuss recent advances in our understanding of the role of secreted vesicles in cardiac repair, with a focus on CPC-derived exosomes.

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“…The CADUCEUS clinical trial showed that intracoronary administration of autologous CDCs decreased scar size, increased viable myocardium and improved regional function in infarcted myocardium (Makkar et al, 2012; Malliaras et al, 2014). Recently, in a post-infarct heart failure model, CPC-derived exosomes enhanced recovery of cardiac function, supporting the biological activities attributed to these extracellular vesicles (Kervadec et al, 2016). …”

Section: Exosomal Mirnasmentioning

confidence: 73%

Exosomes: A Rising Star in Failing Hearts

Chen

Yang

2017

Front. Physiol.

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Although exosomes were previously recognized as a mechanism for discharging useless cellular components, growing evidence has elucidated their roles in conveying information between cells. They contribute to cell–cell communication by carrying nucleic acids, proteins and lipids that can, in turn, regulate behavior of the target cells. Recent research suggested that exosomes extensively participate in progression of diverse cardiovascular diseases (CVDs), such as myocardial infarction, cardiomyopathy, pulmonary arterial hypertension and others. Here, we summarize effects of exosome-derived molecules (mainly microRNAs and proteins) on cardiac function, to examine their potential applications as biomarkers or therapeutics in CVDs.

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Cardiovascular progenitor–derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure

Cited by 176 publications

References 35 publications

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

Exosomes: A Rising Star in Failing Hearts

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