Foundation-funded study identifies lupus related gene that affects adult stem cells
It is thought that lupus may result from defective and over reactive immune cells. The bone marrow produces a type of cell called mesenchymal stem cells or mesenchymal stromal cells (MSCs) that have the capacity to off-set the effects of the over reactive immune cells. However, it is believed that mesenchymal stem cells that do not work properly may contribute to disease in the people with lupus who produce them and should not be used in mesenchymal stem cell treatment for lupus.
Now, new research conducted by 2013 Lupus Foundation of America Adult Stem Cell Research grantee Laurence Morel, PhD (Whisenant Family Professor of Pathology and Director of the Experimental Pathology Division at the University of Florida College of Medicine) and her team studied whether mesenchymal stem cells that carry the lupus susceptibility gene Pbx1 would be defective, potentially contributing to lupus and inhibiting their ability to be used in therapy.
Until now, researchers did not have insight into which genes regulate the immune controlling functions of mesenchymal stem cells. Previous studies have shown that this gene makes immune cells more aggressive in lupus-prone mice and also plays a major role in regulating stem cell function. Other research conducted in both mice and humans has also shown that there is a link between the Pbx1 gene and an increased likelihood of developing lupus.
Dr. Morel’s research findings, made possible with support from the Lupus Foundation of America, were recently published in the Journal of Immunology, a leading peer-reviewed journal featuring novel findings in all areas of experimental immunology, including both basic and clinical studies.
“This is, to our knowledge, the first study to identify a gene that regulates the immune controlling functions of mesenchymal stem cells,” explains Dr. Morel. “Moreover, it is the first study to identify a lupus related gene that affects mesenchymal stem cells. This study may contribute to advancing mesenchymal stem cells cellular therapies in lupus, not only by providing a better understanding of how they work, but also by genetic screening to identify optimal mesenchymal stem cells to be used for therapy.”
Dr. Morel adds: “As a next step, we are seeking additional funding to understand the mechanism by which Pbx1 regulates the function of mesenchymal stem cells in mice and humans and to test how to restore the normal functions of mouse and human lupus mesenchymal stem cells to be used in cellular therapy.”
Researchers in this study used mice to assess whether these genes affect the function of stem cells in a way that alters their ability to be therapeutic. Additional research in this area is needed to determine if the information can be translated into human studies, possibly enabling clinicians to predict who may benefit from stem cell therapy.
The Lupus Foundation of America has been a pioneer in advancing basic and clinical adult stem cell transplantation research in humans as a treatment for lupus. We continue to break new ground through the funding of research such as Dr. Morel’s study to better understand the role of adult stem cells in treating lupus and severe manifestations of the disease.