Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling.

Autor: Anderson JD; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Johansson HJ; Cancer Proteomics, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Graham CS; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Vesterlund M; Cancer Proteomics, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Pham MT; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Bramlett CS; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Montgomery EN; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Mellema MS; Surgical and Radiological Sciences, Department of Veterinary Medicine, University of California Davis, Davis, California, USA., Bardini RL; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Contreras Z; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Hoon M; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Bauer G; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Fink KD; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Fury B; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Hendrix KJ; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA., Chedin F; Department of Molecular and Cellular Biology, University of California Davis, Davis, California, USA., El-Andaloussi S; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom., Hwang B; Department of Surgery, University of Washington, Seattle, Washington, USA., Mulligan MS; Department of Surgery, University of Washington, Seattle, Washington, USA., Lehtiö J; Cancer Proteomics, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Nolta JA; Stem Cell Program, Department of Internal Medicine, University of California Davis, Davis, California, USA.
Jazyk: angličtina
Zdroj: Stem cells (Dayton, Ohio) [Stem Cells] 2016 Mar; Vol. 34 (3), pp. 601-13. Date of Electronic Publication: 2016 Feb 19.
DOI: 10.1002/stem.2298
Abstrakt: Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.
(© 2016 AlphaMed Press.)
Databáze: MEDLINE
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