Reparative function of resident mesenchymal stem cells
The focus of our work is to understand how the reparative function of resident lung mesenchymal stem cells (MSC) is altered during the development and course of lung diseases including pulmonary hypertension, fibrosis and emphysema. In order to define a role for lung MSC in the context of lung disease and their regulation by the microenvironment we employ mouse models. Additionally we use patient derived induced pluripotent stem cells (iPS) as a cell based model to understand molecular changes in which occur in mesenchyme and vascular cell populations as a result of disease specific gene mutations.
Our laboratory has identified and characterized lung MSC and demonstrated that these cells are present in the distal lung associated with the microvasculature in both mouse and human tissue. Recent studies in our lab have shown that proper function of the lung MSC is that of an adult angioblast which plays a role in maintaining vascular integrity. Loss of proper MSC function results in loss of tissue integrity and function.
There is an increasing emphasis on the development of cell-based therapies to address these conditions, but the lung is a recalcitrant candidate for these strategies because of the diverse cell types and functions as well as a lack of understanding of how chronic disease processes affect stem cell differentiation. Therefore, prior to testing cell-based therapy, it is desirable to use pre-clinical models of lung injury and chronic disease to determine how changes in the lung tissue during the development of disease affect resident stem cell differentiation and function.