Investigate the Function and Mechanism of Hypoxia Preconditioned-Human Umbilical Cord Warton$S Jelly Mesenchymal Stem Cells in Ameliorating Elastase-Induced Pulmonary Emphysema.

Chronic obstructive pulmonary diseases (COPD) is characterized by an abnormal inflammatory response in the lung and subsequent secretion of active neutrophil serine proteases to break down connective tissue components. To date, there is no effective treatment for emphysema. Recently, the advancement of mesenchymal stem cells (MSCs) therapy has shed the light on improving the treatment of emphysema. Our preliminary results and others reports indicated that MSCs can be engrafted at the injury sites and reduce the damage of the alveoli in mouse model of elastase-induced emphysema. However, the beneficial effect is limited because the amount of engrafted MSCs decreased dramatically by 24 hr after transplantation. Therefore, increasing the survival duration of engrafted MSCs is a prerequisite for the success of stem cell therapy of emphysema. Recently, our publication demonstrated that hypoxia-preconditioned mouse MSCs significant improves the therapeutic effect of the bleomycin-induced pulmonary fibrosis in mouse model. The long term objective of our research is to develop an efficacious treatment regimen for emphysema. In this proposed research project, we aim to establish a standard operating procedure (SOP) for emphysema therapy using human umbilical cord Warton’s Jelly MSCs (WJ-MSCs) as therapeutic materials since they have better therapeutic potential than other MSCs. we hypothesize that hypoxia preconditioning of WJ-MSC (HMSC) transplantation leads to transient engraftment and secretion of factor(s) 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 is designed to establish and characterize the hypoxia-preconditioned WJ-MSCs. We will establish an SOP that allows us to efficiently generate hypoxia-preconditioned WJ-MSCs for in vitro and in needs. Furthermore, the protective effect of hypoxia preconditioned WJ-MSCs will be tested using elastase-induced emphysema mouse model. Secondly, the underlying molecular mechanisms of the protective effect of hypoxia preconditioned WJ-MSCs will be investigated in specific aim 2 and aim 3. 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 hypoxia preconditioned WJ-MSCs in ameliorating elastase-induced pulmonary emphysema but also will lead a new avenue of therapy for COPD.

Project ID:PC10507-0276
External Project ID:MOST105-2314-B182-042-MY3