Adipose-derived stem cells attenuate rheumatoid arthritis by restoring CX3CR1+ synovial lining macrophage barrier

作者：Lei Wang, Ming Hao, Yongyue Xu, Zhaoyan Wang, Hanqi Xie, Bo Zhang, Zhang Xue, Jun Lin, Xiaodan Sun, Jianbin Wang, Qiong Wu · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04144-5 · 被引用次数：13 · 研究领域：Extracellular vesicles in disease、Mesenchymal stem cell research、Immune cells in cancer

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease and the integrity of CX 3 CR1 + synovial macrophage barrier significantly impacts its progression. However, the mechanisms driving the dynamic changes of this macrophage barrier remain unclear. Traditional drug therapies for RA have substantial limitations. Mesenchymal stem cells (MSCs)-based cell therapy, especially adipose-derived stem cells (ADSCs), hold therapeutic promise. Nevertheless, the underlying therapeutic mechanism of ADSCs, especially their interactions with CX 3 CR1 + macrophages, require further investigation. Methods To explore the interaction between ADSCs and CX 3 CR1 + synovial macrophages during barrier reconstruction, underlying the therapeutic mechanism of ADSCs and the mechanisms on the dynamic changes of the macrophage barrier, scRNA-seq analysis was conducted 4 days after ADSCs injection in serum transfer-induced arthritis model mice. The roles of mitochondria transfer and ADSCs transplantation were also explored. Bulk RNA-seq analysis was performed after the co-culture of ADSCs and CX 3 CR1 + synovial macrophages. To study the in vivo fate of ADSCs, bulk RNA-seq was performed on ADSCs retrieved at 0, 2, 4, and 7 days post-injection. Results Intra-articular injection of ADSCs effectively attenuated the pathological progression of mice with serum transfer-induced arthritis. ADSCs gradually adhered to CX 3 CR1 + macrophages, facilitating the restore of the macrophage barrier,...