Westley Reeves, MD, University of Florida
"Generation of Regulatory T Cells in Lupus Using Mesenchymal Stem Cells"
2008 Novel Pilot Projects Program
This grant award is provided by funds contributed through a trust created in memory of Stephen and Catherine Pida
Mesenchymal stem cells (MSC) are adult stem cells that can be isolated from the bone marrow or other tissues. They have the useful property of being immunosuppressive and potentially can be used to stimulate the production of regulatory T lymphocytes. We found that they increase the expression of a protein important for the development of these regulatory cells called Foxp3 and that increased Foxp3 expression is associated with the downregulation of autoantibodies in mice with lupus. Since MSC are easy to grow in culture and are readily amenable to gene therapy, we propose to exploit these unique properties to direct immunosuppressive (regulatory) T cells to affected tissues in lupus. Mice with lupus will be treated with MSC to see if we can turn off the production of lupus autoantibodies and reverse or prevent the development of inflammatory disease in the kidneys (lupus nephritis) and lungs (pulmonary vasculitis). If successful, the same approach could be translated readily into humans. In the future, MSC could be isolated from adult bone marrow, blood, or adipose tissue (fat), modified (if necessary) using gene therapy, and reinfused into patients as a treatment for the inflammatory manifestations of SLE.