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

医学 类风湿性关节炎 内科学 间充质干细胞 痹症科 滑膜炎 脐带 移植 关节炎 胃肠病学 外科 免疫学 病理
作者
Xiao He,Yi Yang,Mengwei Yao,Lei Yang,Luoquan Ao,Xueting Hu,Li Zhan,Xiaofeng Wu,Yan Tan,Wei Wang,Wei Guo,Joseph A. Bellanti,Song Guo Zheng,Xiang Xu
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:79 (10): 1298-1304 被引量:57
标识
DOI:10.1136/annrheumdis-2020-217798
摘要

Objectives To 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). Methods Study 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. Results In 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. Conclusions The 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.
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