Exploring Mesenchymal Stem Cell-Based Treatment to Sustain Renal Functions in Chronic Lupus Nephritis

Concept: Therapies that use stem cells, which can develop into virtually any cell type, are new exciting treatment possibilities for severe and life-threatening autoimmune diseases, diseases in which the body attacks itself. Although stem cells are known to have significant healing and repair capabilities and can affect the immune system response, little is known about the use of stem cells to treat autoimmune diseases in clinical trials. This project will test a new procedure in which stem cells are injected directly into the kidney. The experiments will use a well-studied mouse model that is uniquely suited for studying autoimmune kidney disease. This approach has the potential to be an efficacious, but cost-effective, approach that could improve dramatically the quality of life of lupus patients who are likely, without this treatment, to need dialysis or kidney transplantation. Furthermore, advancing knowledge on the mechanisms of kidney tissue repair and healing is important in the design of future treatments and identifying factors to predict disease progression. This will be examined by incorporating studies on resident kidney stem cells (organ-specific multi-potent stem cells), properties of donor stem cells, and the inflammatory microenvironment in the treatment groups.

Objective: The primary objective of this research is to test the ability of stem cells, when injected directly into the target organ, to promote tissue healing and repair in the chronic kidney disease in experiments that use mice that are designed to mimic lupus. A secondary objective of this project is to test whether the properties or numbers of kidney stem cells can predict risk for progress toward kidney failure. Finally, the project is important as the first step in establishing collaborations with internationally recognized centers of excellence toward future studies of stem cells and autoimmune diseases.

Innovative Aspect of the Project: The innovative aspect of the project is applications of targeted cellular engineering to save organ function in patients with systemic lupus erythematosus (SLE or lupus). Neither disease control by delivery of stem cells directly into kidney tissue nor systematic examination of kidney stem cells has been reported. This work lays a foundation for kidney repair and tissue replacement using a treatment in which stem cell are injected directly into the kidney. The availability of a unique and promising stem cell line and the collaboration of scientists with expertise using these cells will optimize the likelihood of success.

Relevance: The objective of this research is compatible with the interests of the Walter Reed Army Medical Center in regenerative medicine, the medical field of healing and tissue repair, and cost-effective treatments. Military spending for treatment of chronic diseases is substantial and patients with advanced lupus nephritis require comprehensive medical care. Many such patients are progressing toward permanent kidney failure requiring dialysis or kidney transplant. The project is a start for a productive line of research using stem cells in autoimmune diseases in collaborations with leading centers using innovative knowledge. Research and development in stem cell-based treatments has practical and humanitarian objectives that are in line with our obligations to these patients.