Accepting PhD Students

PhD projects

Nebulised Mesenchymal Stem Cell (MSC) Products for Acute Respiratory Distress Syndrome (ARDS). Recent data from NUIG and elsewhere have proposed MSCs as a possible medicine for ARDS. Despite progression to clinical trials in the USA and UK, there remains concerns as to the production, storage and delivery of allogeneic cells to the patient, while the MSC secretome alone may prove to recapitulate these beneficial effects.Here we will take the novel approach of nebulisation of MSC or MSC products directly to the lung as a possible therapy for ARDS. In conjunction with our partners at Aerogen Inc, Galway, we will use off-the-shelf and custom engineered vibrating mesh nebulisers to deliver MSC conditioned media (CM), MSC derived microvesicle (MV) preps, or whole MSC cells to pre-clinical models or ARDS. Task 1: Degradation analysis of the nebulised MSC secretome. CM or MV preparations derived from bone marrow, umbilical cord and adipose tissue derived MSCs will be passed through a range of vibrating mesh nebulisers. Total protein PAGE and ELISA of known MSC effect mediators will be performed. MV integrity will be analysed by gold-labelled antibody SEM. Task 2: In vitro analysis of the nebulised MSC secretome. CM or MV preparations will be nebulised and used in standard in vitro assays of MSC function, such as T-cell proliferation assay and examination of anti-inflammatory and wound healing effects in primary lung epithelial cell culture. Task 3: Physical characterisation of the nebulised MSC secretome. CM or MV preparations will be nebulised and analysed for droplet size (particle size analyser), delivery to the lung (breathing simulator) and dispersion (impactor). Retrieved samples will be examined as in Task 1 and Task 2. Task 4: The Nebulised MSC secretome in ARDS and fibrosis. CM or MV preparations will delivered via nebulisation to rat E.coli and bleomycin models of lung disease. Oxygenation, compliance, lung structure and inflammatory response will be assessed. Fibrosis will be assessed by Micro-CT Task 5: Nebulisation of whole MSC. MSC will be passed through modified large pore nebulisers and assessed for viability and in vitro therapeutic activity as in Task 2. They will then be delivered intratracheally by nebuliser to in vivo lung disease models as in Task 4.