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.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Mellows B,Mitchell R,Antonioli M,Kretz O,Chambers D,Zeuner MT,Denecke B,Musante L,Ramachandra DL,Debacq-Chainiaux F,Holthofer H,Joch B,Ray S,Widera D,David AL,Huber TB,Dengjel J,De Coppi P,Patel Kdoi
10.1089/scd.2017.0089subject
Has Abstractpub_date
2017-09-15 00:00:00pages
1316-1333issue
18eissn
1547-3287issn
1557-8534journal_volume
26pub_type
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