People with lupus, an autoimmune disease, suffer from fatigue, joint pain, and swelling, and also have a markedly increased risk of developing osteoporosis. Clinical trials have shown that receiving a mesenchymal stem cell transplant (MSCT) can greatly improve the condition of lupus patients, yet it has not been clear why this treatment strategy works so well. Now, University of Pennsylvania (Penn) researchers, and colleagues, have puzzled out a mechanism by which stem cell transplants may help preserve bone in an animal model of lupus. In a paper published in the October 6, 2015 issue of Cell Metabolism, the research team shows that the transplanted cells provide a source (exosomes) of a key protein called Fas, which improves the function of bone marrow stem cells through a multi-step, epigenetic effect. The work has implications for potential therapeutic strategies for lupus, as well as other diseases for which stem cell transplants have shown promise. “When we used stem cells for these diseases and put them into the circulation, we didn’t know exactly what they were doing, but saw that they were very effective,” said Songtao Shi (photo), D.D.S., Ph.D., Chair and Professor of the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine and a co-corresponding author on the paper. “Now we’ve seen, in a model of lupus, that bone-forming mesenchymal stem cell function was rescued by a mechanism that was totally unexpected.” Dr. Shi collaborated on the work with Shiyu Liu, Dawei Liu, Chider Chen, and Ruili Yang of Penn Dental Medicine; Kazunori Hamamura, Alireza Moshaverinia, and Yao Liu of the University of Southern California; and co-corresponding author Yan Jin of China’s Fourth Military Medical University.
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