Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial…

By F. Arslan, R. C. Lai, M. Smeets, Lars Akeroyd, A. Choo, E. Aguor, L. Timmers, H. V. van Rijen, P. Doevendans, G. Pasterkamp and 2 more. Stem Cell Research, 2013

1,013 citations recorded by the source corpus.

We have previously identified exosomes as the paracrine factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30 min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5 min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28 days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.

Subfields: Electrical and Electronic Engineering, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/7b74d48f58060018c1d71f44e11ed9d2bba50a82

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Citations in the corpus

Influence of storage condition on exosome recovery (2016, neutral): “a therapeutic agent [19,22], disease biomarker [5,8] and drug delivery vehicle [23].”
Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. (2015, neutral): “phosphorylated-Akt and phosphorylated-GSK-3β (65)”
Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy (2014, background): “Exosomes transfer proteins and RNA (Lugini et al., 2012), notably microRNAs (miRNAs) (Zhu and Fan, 2011), from cell to cell, rationalizing potential applications in clinical therapeutics (Arslan et al., 2013; Hergenreider et al., 2012; O’Loughlin et al., 2012).”
Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, methodology): “[285] demonstrated a similar reduction in infarct size in a model of I/R following the administration of MSC-derived exosomes, 5 min prior to reperfusion.”
Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. (2015, positive): “Here, we present a systematic comparison study between a robust EV purification method, ultrafiltration with size-exclusion liquid chromatography (UF-LC), adapted from previous studies, 14 – 16 and UC.”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “MSC-derived exosome treatment reduces inflammation after I/R by decreasing neutrophil and macrophage infiltration [134].”
Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, positive): “They not only participate in the process of tissue repair and injury, 24,25 and have certain therapeutic effects on cardiovascular diseases (like myocardial infarction) 26,27 and neurological diseases, 28 but also can alleviate liver injury and be used in the treatment of liver diseases.”
Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction (2015, background): “of reduction in oxidative stress and AKT activation in a MI model.(17) Similarly, exosomes secreted by CPCs were reported to stimulate migration of endothelial cells(18) and protect ischemic myocardium from ischemia/reperfusion injury(19)”