Laurence Morel, PhD, University of Florida College of Medicine

“Genetic Regulation of Stem Cell Dysfunction in a Mouse Model of Lupus”

2013 Adult Stem Cell Grant Award

This grant is in honor of The Cooper Family Foundation.

There is abundant evidence that lupus is a disease caused by defects in cells coming from the bone marrow. In addition to the role of blood cells in lupus, adult bone marrow stem cells are often defective in people with lupus and in mouse models of lupus. Two types of bone marrow stem cells have been implicated: hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs).

Stem cell treatments with either HSCs or MSCs have been used for people with severe, life-threatening cases of lupus. Self (autologous) bone marrow transplants with HSCs has been reported to be successful in about 50% of the cases by “resetting the system,” replacing defective inflammatory leukocytes with new ones. The results of the few cases of severe lupus that have been treated with MSCs are mixed.

To better understand why some people with severe lupus benefit from this type of treatment while others do not, Dr. Morel and her team will study two lupus susceptibility genes, Pbx1 and p18, that make T and B immune cells more aggressive in both lupus-prone mice and people with lupus and that are also important in stem cell biology. The researchers will use mice to assess whether these genes affect the function of stem cells in a way that alters their therapeutic value. This study has potential to be translated into human studies, possibly enabling clinicians to predict who might benefit from stem cell therapy.