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Stem Cells Dev. 2017 Sep 15;26(18):1316-1333. doi: 10.1089/scd.2017.0089. Epub 2017 Aug 22.

Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis.

Author information

1
1 School of Biological Sciences, University of Reading , Reading, United Kingdom .
2
2 Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases IRCCS 'Lazzaro Spallanzani' , Rome, Italy .
3
3 Department of Medicine III, Faculty of Medicine, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
4
4 Renal Division, Faculty of Medicine, Medical Centre, University of Freiburg , Freiburg, Germany .
5
5 Department of Medicine IV, Faculty of Medicine, University of Freiburg , Freiburg, Germany .
6
6 Wolfson Centre for Age-Related Diseases, King's College , London, United Kingdom .
7
7 School of Pharmacy, University of Reading , Reading, United Kingdom .
8
8 Interdisciplinary Centre for Clinical Research Aachen, RWTH Aachen University , Aachen, Germany .
9
9 Centre for Bioanalytical Sciences (CBAS), Dublin City University , Dublin, Ireland .
10
10 Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health , London, United Kingdom .
11
11 URBC, Namur Research Institute for Life Science (NARILIS), University of Namur , Namur, Belgium .
12
12 FRIAS Freiburg Institute for Advanced Studies, University of Freiburg , Freiburg, Germany .
13
13 Micregen, Biohub, Cheshire, United Kingdom .
14
14 Institute for Women's Health, University College London , London, United Kingdom .
15
15 NIHR University College London Hospitals Biomedical Research Centre , London, United Kingdom .
16
16 BIOSS Centre for Biological Signalling Studies and Centre for Systems Biology (ZBSA), Albert-Ludwigs University , Freiburg, Germany .
17
17 Department of Biology, University of Fribourg , Fribourg, Switzerland .

Abstract

The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration, and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly, we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EVs) that harbor much, but not all, of the biological activity of the whole secretome. Proteomic characterization of the EV and free secretome fraction shows the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly, we show that the EVs only contain miRNA and not mRNA. This suggests that tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than imposing new, signaling pathways. The EVs harbor significant anti-inflammatory activity as well as promote angiogenesis, the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury.

KEYWORDS:

miRNA; muscle; regeneration; secretome

PMID:
28679310
DOI:
10.1089/scd.2017.0089
[Indexed for MEDLINE]

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