When routine repair mechanisms fail to regenerate severe burn wounds, mesenchymal stem cell therapy is considered. However, engrafted mesenchymal stem cells are prone to become myofibroblasts when exposed to high mechanical tension and pro-fibrotic cytokines in the wound microenvironment. Myofibroblast activity increases wound stiffness and activates healthy precursor cells into destructive phenotype, resulting in pathological remodelling and hypertrophic scarring. Using soft silicone substrates with near-physiological stiffness, I tested the hypothesis that myofibroblast characteristics acquired by mesenchymal stem cells in cell culture are preserved by microRNA modifications typical for fibrosis and demonstrated that priming mesenchymal stem cells on soft substrates protect them from subsequent activation and that the mechanically propagated myofibroblast memory is mediated by miR-21. This study aims to demonstrate that suppressing myofibroblast activation will maximize and prolong the beneficial regenerative effects of mesenchymal stem cells while terminating harmful and excessive tissue remodelling characteristic for fibrosis upon engraftment.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/44039 |
| Date | 18 March 2014 |
| Creators | Li, Chen |
| Contributors | Hinz, Boris |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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