Grant: Project Grant

Fibrosis is a process defined as persistent and abnormal wound healing resulting in loss of organ function and often death. Fibrosis contributes to almost one third of deaths in developed countries. Unfortunately, there is no cure for fibrosis. We have studied mesenchymal stromal cells (often called stem cells or MSCs) and we have found that they interfere with the development of fibrosis and can contribute to reversing fibrosis in cultured cells. We hypothesize that MSCs and their products have anti-fibrotic properties in an animal model of lung and skin fibrosis as well as in patients with scleroderma who have generalized organ fibrosis. We also propose that the effects of MSC or their secreted products result from the elimination or deactivation of the cells that cause fibrosis (myofibroblasts and inflammatory macrophages). We propose to test the effects of the MSCs and their secreted products on skin and lung fibrosis using both human skin and pieces of human lung. We will also study a mouse model treated with bleomycin, a drug that causes skin and lung fibrosis. Effects of the proposed treatments on the interaction between macrophages and myofibroblasts in the skin and lungs of the mouse with fibrosis will be studied. Finally, we propose to study the skin of patients with scleroderma that are currently in a clinical trial of MSC treatment. We will examine the skin for specific markers that are associated with resolution of fibrosis to better understand the cause of this disease and how to treat it. Expertise: Our team has worked, published and co-supervised students together and has the required expertise to accomplish the proposed work. Expected Outcomes: This project will help understand the mechanisms involved in lung and skin fibrosis prevention and resolution following MSC administration. This knowledge is crucial for the optimization of MSC therapies and the development of new antifibrotic approaches.