Application of Novel Subpopulation of Mesenchymal Stem Cells and Its Derived Exosome for Treatment of Elastase-Induced Pulmonary Emphysema Mouse Model

Chronic Obstructive Pulmonary Disease (COPD) is an irreversible and progressive airway obstruction disease, often caused by long-term tobacco smoking, air pollution and other risk factors, which triggers an abnormal chronic inflammatory response in the lung. Currently, COPD ranks seventh among the top ten most common cause of death in Taiwan. Because of the increased oxidative stress leads to extensive cellular damage and injury, oxidants produced by the lung epithelium, and inflammatory cells in emphysema pathophysiology play an important role. To date, there is an urgent need to develop a novel therapeutic strategy for the COPD patient. Recently, our laboratory also demonstrated that the transplantation of genetically modified stem cells (MSC) or MSC-predifferentiated lung epithelial progenitor-like cells showed significantly improved elastase-induced mouse emphysema model. Furthermore, preconditioned-MSCs significant improves the therapeutic effect of the bleomycin-induced lung fibrosis through the paracrine effects. Studies indicated that several subpopulations isolated from heterogeneous MSCs have been demonstrated that providing a better therapeutic effects for specific therapies in regenerative medicine applications. Recent data also suggest that exosomes released from MSCs and present in medium can lead to protective effects similar to those of MSCs. Taken together, In order to improve and enhance the therapeutic efficacy of MSC in the mouse emphysema model, we developed a novel method for isolating of subpopulation cells and its exosomes from MSC, we hypothesize that subpopulations of MSCs transplantation leads to transient engraftment and secretion of factor(s) or its derived exosomes that partly contribute anti-inflammatory effects via suppress the NLRP3 inflammasome activation from elastase-induced emphysema. Two intertwined specific aims are proposed to carry out this project. Specific aim one and three are designed to establish and characterize the subpopulations of MSCs and its derived exosomes. Furthermore, the protective effect of the subpopulations of MSCs and its derived exosomes will be tested using elastase-induced emphysema mouse model. Secondly, the underlying molecular mechanisms of the protective effect of subpopulations of MSCs will be investigated in specific aim 2. We anticipate to completing this proposed project within three years. Preliminary studies have generated exciting data to support our hypothesis. We believe that this study not only can improve our understanding of the mechanism of novel subpopulation of mesenchymal stem cells and its derived exosomes in ameliorating elastase-induced pulmonary emphysema but also will lead a new avenue of therapy.

Project ID:PC10901-1753
External Project ID:MOST108-2314-B182-052-MY3