USC University of Southern California

Mesenchymal Stem Cell Infusions Reverse Lupus Complications

Systemic lupus erythematosus, or lupus, is a serious disease that literally turns the body’s immune system against itself and affects the entire body, especially the skin, kidneys, nervous system, and joints. The common treatments used to slow the disease’s assault on patients’ bodies involve immunosuppressive drugs, which alleviate lupus symptoms for many patients but leave them vulnerable to potentially devastating infections and organ dysfunction.

New stem cell research from the School of Dentistry’s Center for Craniofacial Molecular Biology and a resulting human clinical trial from China’s Nanjing University hold great promise for lupus patients, said Songtao Shi, School of Dentistry associate professor. The study, “Mesenchymal Stem Cell Transplantation Reverses Multi-Organ Dysfunction in Systemic Lupus Erythematosus Mice and Humans,” appeared online in Stem Cells this month.

Lupus isn’t just the result of malfunctioning immune system cells, Shi said. Those cells appear to have a close relationship with mesenchymal stem cells, or MSC, in bone marrow, which differentiate into several types of cells that can affect the immune system.

“These stem cells live in the bone marrow along with the immuno cells,” he said. “There’s a lot of interplay going on; if the immuno cells have problems, the MSC or the interplay between the two types of cells may have problems as well.”

While observing mice whose MSC function had been impaired, CCMB researchers noticed that the stem cell’s deficiencies appeared to be partially responsible for the development of a lupus-like disease in the animals. After the infusion of healthy MSC into the experimental group of mice, their symptoms abated and organ function improved. These improvements were much more dramatic than those seen in the mice undergoing the traditional treatment of immune system suppression.

Fueled by CCMB’s promising laboratory results, researchers investigating lupus at Nanjing University Medical School used MSC infusion to treat four young adult patients whose lupus symptoms no longer responded well to immunosuppression therapy. The three women and one man – nearly 90 percent of SLE patients are female – were each suffering from kidney complications as a result of the disease and received healthy stem cells from bone marrow donated by immediate family members.

In all of the patients, organ function improved greatly, with two patients lessening their dosages of immunosuppressive drugs to low maintenance levels, and the other two stopping their immunosuppression regimen entirely. Short-term follow-up at 18 months post-MSC infusion indicated no problems with either organ function or reactions to the transplanted cells, Shi said. While 5-to-10-year follow-up still needs to be completed, the results of the single stem cell treatment are incredibly promising.

“Time will tell, but we feel very good about this work,” he said.

Being among the first scientists to target immunodisease with a mesenchymal stem cell approach is exciting, Shi added. Also, the uniquely close partnership between the basic stem cell scientists at USC and the clinical researchers investigating lupus at Nanjing University is one that Shi hoped was recreated with investigations into other diseases in order to more quickly get promising treatments to the patients that need them.

“In the future, this type of research will help us to understand diseases and find cures faster,” Shi said.