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

• Type of Material: Article
• Authors: Diane L. Kamen, Medical University of South Carolina; Caroline Wallace, Medical University of South Carolina; Zihai Li, Ohio State Wexner Medical Center; Megan Wyatt, Emory University; Chrystal Paulos, Emory University; Chungwen Wei, Emory University; Hongjun Wang, Medical University of South Carolina; Bethany J. Wolf, Medical University of South Carolina; Paul J. Nietert, Medical University of South Carolina; Gary Gilkeson, Medical University of South Carolina
• Language: English
• Date: 2022-07-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2022.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/lupus-2022-000704
• Title of Journal or Parent Work: LUPUS SCIENCE & MEDICINE
• Volume: 9
• Issue: 1
• Grant/Funding Information: This study was funded by a grant from the Lupus Foundation of America and NIH UL1 RR029882
• Keywords: TRANSPLANTATION; PROLIFERATION; STEROID-RESISTANT; STEM-CELLS; Science & Technology; CRITERIA; SUPPRESSION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; THERAPY; Rheumatology; VERSUS-HOST-DISEASE; PHENOTYPE; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Cell; Health Sciences, Obstetrics and Gynecology

Abstract

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 1×10 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 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.