Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 79; no. 10; pp. 1298 - 1304
• Main Authors: He, Xiao, Yang, Yi, Yao, Mengwei, Yang, Lei, Ao, Luoquan, Hu, Xueting, Li, Zhan, Wu, Xiaofeng, Tan, Yan, Xing, Wei, Guo, Wei, Bellanti, Joseph A, Zheng, Song Guo, Xu, Xiang
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.10.2020; Elsevier Limited
• Subjects: Adult; Animal models; Animals; Ankle; Arthritis, Experimental; arthritis, rheumatoid; Arthritis, Rheumatoid - therapy; Autoimmune diseases; Biological products; Cartilage; Cell cycle; Collagen; Combined Modality Therapy - methods; Cord Blood Stem Cell Transplantation - methods; Cytokines; Disease; Erythema; Female; Humans; Immunologic Factors - therapeutic use; Immunology; inflammation; Interferon-gamma - therapeutic use; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchyme; Mice; Middle Aged; Nonsteroidal anti-inflammatory drugs; Patients; Recombinant Proteins - therapeutic use; Rheumatoid arthritis; Rheumatology; Stem cells; Synovitis; therapeutics; Transplantation; Umbilical cord; γ-Interferon; inflammation; arthritis, rheumatoid; therapeutics
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2020-217798

ObjectivesTo clarify the key role of circulating interferon-γ (IFN-γ) and to improve the clinical efficacy of mesenchymal stem cell (MSC) transplantation (MSCT) in patients with rheumatoid arthritis (RA).MethodsStudy of wild-type or IFN-γR-/- MSCT was first evaluated in a murine model of collagen-induced arthritis (CIA) following which a phase 1/2 randomised controlled study was conducted in 63 patients with RA who responded poorly to regular clinical treatments. Subjects were randomly assigned to an MSCT monotherapy group (n=32) or an MSCT plus recombinant human IFN-γ treatment group (n=31), with 1 year of follow-up. The primary end points consisted of efficacy as assessed as good or moderate EULAR response rates and the proportion of patients at 3 months attaining American College of Rheumatology 20 (ACR20) response rates.ResultsIn the murine studies, wild-type MSCT significantly improved the clinical severity of CIA, while IFN-γR-/- MSCT aggravated synovitis, and joint and cartilage damage. Transitioning from the murine to the clinical study, the 3-month follow-up results showed that the efficacy and ACR20 response rates were attained in 53.3% patients with MSCT monotherapy and in 93.3% patients with MSCT combined with IFN-γ treatment (p<0.05). No new or unexpected safety issues were encountered in 1-year follow-up for either treatment group.ConclusionsThe results of this study show that IFN-γ is a key factor in determining the efficacy of MSCT in the treatment of RA, and that an MSC plus IFN-γ combination therapeutic strategy can greatly improve the clinical efficacy of MSC-based therapy in RA patients.