King's College London

Research portal

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

Research output: Contribution to journalArticle

Ben Mellows, Robert Mitchell, Manuela Antonioli, Oliver Kretz, David Chambers, Marie Theres Zeuner, Bernd Denecke, Luca Musante, Durrgah L. Ramachandra, Florence Debacq-Chainiaux, Harry Holthofer, Barbara Joch, Steve Ray, Darius Widera, Anna L. David, Tobias B. Huber, Joern Dengjel, Paolo De Coppi, Ketan Patel

Original languageEnglish
Pages (from-to)1316-1333
Number of pages18
JournalSTEM CELLS AND DEVELOPMENT
Volume26
Issue number18
Early online date22 Aug 2017
DOIs
Accepted/In press3 Jul 2017
E-pub ahead of print22 Aug 2017
Published15 Sep 2017

King's Authors

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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454