Investigation of efficacy and mechanisms of action in mesenchymal stromal cell therapy for chronic lung diseases

Mesenchymal Stromal Cells (MSC) are adult multipotent cells that possess self-­‐renewal and regenerative capacities, with the ability to differentiate into a variety of cell types. They have potent immunosuppressive abilities, facilitating the use of allogeneic MSC as a cellular therapy. Functionally, it is the trophic mediated effects of MSC that have become the focus of research due to paracrine mediated tissue reparative and protective effects. This study has examined the use of MSC for the treatment of inflammatory and fibrotic lung diseases, specifically Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF). In vitro characterisation of MSC demonstrated significant cytoprotective and reparative effects, through inhibition of epithelial apoptosis, suppression of neutrophil functions and repair of injured epithelial cells. These effects were mediated by MSC production of HGF and subsequent paracrine signalling. Utilising a humanised mouse model of COPD, MSC administration resulted in beneficial cytoprotective effects due to HGF, including reduced inflammation, and epithelial apoptosis. These effects were greatest with early MSC administration with reduced efficacy following late MSC administration. In a bleomycin mouse model of fibrosis, MSC again displayed significant cytoprotective effects with early MSC intervention. Decreased epithelial apoptosis and collagen deposition were observed with MSC treatment with HGF demonstrated to be important in this process. The work presented here demonstrates significant protective effects of early MSC treatment in inflammatory and fibrotic lung diseases mediated in part by MSC production of HGF.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2015

Author dc:creator

• Kennelly, Helen

Language dc:language

en