Investigating the efficacy and mechanism of action of mesenchymal stromal cell therapy in burn wound healing

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dc.contributor.advisor Caplice, Noel M. en
dc.contributor.advisor Clover, James en
dc.contributor.advisor McHugh, Peter en Whelan, Derek S. 2018-03-21T12:50:53Z 2017 2017
dc.identifier.citation Whelan, D. S. 2017. Investigating the efficacy and mechanism of action of mesenchymal stromal cell therapy in burn wound healing. PhD Thesis, University College Cork. en
dc.identifier.endpage 225 en
dc.description.abstract Several studies suggest that mesenchymal stromal cell (MSC) therapy may be efficacious in accelerating wound healing. Which source of MSC is therapeutically superior has not been well established, especially in large clinically relevant animal models. We therefore investigated the efficacy of Bone marrow-MSC (BM-MSC) and Adipose-MSC (AD-MSC) in the treatment of burn wounds in a large porcine model. Donor matched allogeneic AD-MSC and BM-MSC were applied onto partial thickness burns within a fibrin hydrogel. MSC therapy was similarly efficacious in both groups, increasing wound closure, angiogenesis and collagen content, associated with increased wound maturity at two weeks. To augment this therapeutic response, priming of MSC with inflammatory cytokines was explored. Administration of MSC primed with TNFα resulted in a significant acceleration of burn wound closure, re-epithelialisation and increased angiogenesis, AD-MSC and BM-MSC were therapeutically equivalent in their response to TNFα. We hypothesised that MSC derived CCL-2 may be involved in the MSC therapeutic effect by facilitating macrophage repolarisation and may also play a role in TNFα pre-treatment as CCL2 is greatly induced by TNFα. To further delineate this mechanism, MSC isolated from CCL-2 deficient mice (CCL-2 KO) were applied to excisional wounds in wild-type (WT) mice. Interestingly, CCL-2 deficiency in MSC completely abrogated the therapeutic response compared to WT MSC. CCL-2 KO MSC were unable to repolarise macrophages to the same extent as WT and this was accompanied by a reduced angiogenesis and re-epithelialisation of the wounds at day 10. TNFα pre-treatment of WT MSC significantly increased therapeutic efficacy, resulting in complete re-epithelisation of all wounds by day 10. CCL-2 KO MSC responded somewhat, with increased CD206+ macrophages and reduced Ly6G+ neutrophils present within the wound, but this biology had no effect on re-epithelialisation. en
dc.description.sponsorship Higher Education Authority (PRTLI5) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2017, Derek S. Whelan. en
dc.rights.uri en
dc.subject Burns en
dc.subject Wound healing en
dc.subject MSC en
dc.title Investigating the efficacy and mechanism of action of mesenchymal stromal cell therapy in burn wound healing en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Restricted to everyone for three years en 2021-03-20T12:50:53Z
dc.description.version Accepted Version
dc.contributor.funder Higher Education Authority en
dc.description.status Not peer reviewed en Biosciences Institute en Medicine en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat E-thesis on CORA only en
dc.internal.conferring Autumn 2017 en

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© 2017, Derek S. Whelan. Except where otherwise noted, this item's license is described as © 2017, Derek S. Whelan.
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