Safety, immunological effects and clinical response in a phase I trial of umbilical cord mesenchymal stromal cells in patients with treatment refractory SLE

Background Reports of clinical improvement following mesenchymal stromal cell (MSC) infusions in refractory lupus patients at a single centre in China led us to perform an explorative phase I trial of umbilical cord derived MSCs in patients refractory to 6 months of immunosuppressive therapy. Methods Six women with a SLEDAI >6, having failed standard of care therapy, received one intravenous infusion of 1x10(6) MSCs/kg of body weight. They maintained their current immunosuppressives, but their physician was allowed to adjust corticosteroids initially for symptom management. The clinical endpoint was an SRI of 4 with no new British Isles Lupus Activity Guide (BILAG) As and no increase in Physician Global Assessment score of >0.3 with tapering of prednisone to 10 mg or less by 20 weeks. Results Of six patients, five (83.3%; 95% CI 35.9% to 99.6%) achieved the clinical endpoint of an SRI of 4. Adverse events were minimal. Mechanistic studies revealed significant reductions in CD27IgD double negative B cells, switched memory B cells and activated naive B cells, with increased transitional B cells in the five patients who met the endpoint. There was a trend towards decreased autoantibody levels in specific patients. Two patients had increases in their Helios+Treg cells, but no other significant T cell changes were noted. GARP-TGF beta complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGF beta increases significantly correlated with changes in SLEDAI scores. Conclusion This phase 1 trial suggests that umbilical cord (UC) MSC infusions are very safe and may have efficacy in lupus. The B cell and GARP-TGF beta changes provide novel insight into mechanisms by which MSCs may impact disease.

Automated summary

In this exploratory phase I trial, umbilical cord derived mesenchymal stromal cells (MSCs) were used to treat refractory lupus patients. The results showed that the treatment was safe and effective, with significant reductions in specific cells and autoantibody levels. The study provides novel insights into the mechanisms by which MSCs impact disease.