TY - JOUR T1 - Safety, immunological effects and clinical response in a phase I trial of umbilical cord mesenchymal stromal cells in patients with treatment refractory SLE JF - Lupus Science & Medicine JO - Lupus Sci Med DO - 10.1136/lupus-2022-000704 VL - 9 IS - 1 SP - e000704 AU - Diane L Kamen AU - Caroline Wallace AU - Zihai Li AU - Megan Wyatt AU - Crystal Paulos AU - Chungwen Wei AU - Hongjun Wang AU - Bethany J Wolf AU - Paul J Nietert AU - Gary Gilkeson Y1 - 2022/07/01 UR - http://lupus.bmj.com/content/9/1/e000704.abstract N2 - 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 1×106 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 naïve 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-TGFβ complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGFβ 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-TGFβ changes provide novel insight into mechanisms by which MSCs may impact disease.Trial registration number NCT03171194.All data relevant to the study are included in the article or uploaded as supplementary information. We are happy to provide any additional data on reasonable request. ER -