Mellows, B;
Mitchell, R;
Antonioli, M;
Kretz, O;
Chambers, D;
Zeuner, M-T;
Denecke, B;
... Patel, K; + view all
(2017)
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.
Stem Cells and Development
, 26
(18)
pp. 1316-1333.
10.1089/scd.2017.0089.
Preview |
Text
Patel_manuscrip(edited)t.pdf - Accepted Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1089/scd.2017.0089 |
| Publisher version: | https://doi.org/10.1089/scd.2017.0089 |
| Language: | English |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Hematology, Medicine, Research & Experimental, Transplantation, Cell Biology, Research & Experimental Medicine, secretome, regeneration, muscle, miRNA, ACUTE KIDNEY INJURY, NF-KAPPA-B, MESSENGER-RNA, MACROPHAGE POLARIZATION, GENE-EXPRESSION, IN-VIVO, EXOSOMES, INFLAMMATION, MICROVESICLES, MECHANISM |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1564904 |
Archive Staff Only
 |
View Item |
