Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy
Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells an...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-01-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897241301703 |
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| author | Guangyang Liu Herui Wang Chenliang Zhang Xin Li Yi Mi Yaoyao Chen Liqiang Xu Li Miao Haomiao Long Yongjun Liu |
| author_facet | Guangyang Liu Herui Wang Chenliang Zhang Xin Li Yi Mi Yaoyao Chen Liqiang Xu Li Miao Haomiao Long Yongjun Liu |
| author_sort | Guangyang Liu |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA. Previous in vitro studies indicate that TNF-α secreted by T cells can activate NF-κB in human MSCs, thereby triggering the immunoregulatory capacity of MSCs in a manner dependent on tumor necrosis factor receptor 1 (TNFR1). Inspired by these findings, we aimed to evaluate whether TNFR1 determine the therapeutic effects of hUC-MSCs on RA. First, we investigated whether TNFR1 is necessary for hUC-MSCs to inhibit TNF-α production of PBMCs, a source of elevated TNF-α in patients. Through coculture experiment, we confirmed that this inhibition was dependent on TNFR1. Subsequently, we administered hUC-MSCs or siTNFR1-MSCs to DBA/1J male mice with collagen-induced arthritis. The results indicated that hUC-MSCs significantly alleviated the pathological features of RA and suppressed the inflammatory cytokines IFN-γ, TNF-α, and IL-6 in peripheral blood, also in a manner dependent on TNFR1 either. Given the dramatic pathologic differences between hUC-MSCs and siTNFR1-MSCs treatments, we questioned whether production of growth factors and chemokines was significantly influenced by TNFR1. Consequently, we stimulated hUC-MSCs or siTNFR1-MSCs through IFN-γ, TNF-α, and IL-6, and profiled growth factors and chemokines in serum, which revealed significant changes of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), as well as chemokines CXCL9, CXCL10, IL-8, and RANTES. In summary, our findings suggest that TNFR1 may determine whether hUC-MSCs will gain abilities of anti-inflammation and tissue regeneration. |
| format | Article |
| id | doaj-art-09dab76b929c463b800db9369892b4b8 |
| institution | Kabale University |
| issn | 1555-3892 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj-art-09dab76b929c463b800db9369892b4b82025-01-20T14:03:20ZengSAGE PublishingCell Transplantation1555-38922025-01-013410.1177/09636897241301703Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis TherapyGuangyang Liu0Herui Wang1Chenliang Zhang2Xin Li3Yi Mi4Yaoyao Chen5Liqiang Xu6Li Miao7Haomiao Long8Yongjun Liu9Stem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaStem Cell Biology and Regenerative Medicine Institution, Yi-Chuang Institute of Bio-Industry, Beijing, ChinaRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA. Previous in vitro studies indicate that TNF-α secreted by T cells can activate NF-κB in human MSCs, thereby triggering the immunoregulatory capacity of MSCs in a manner dependent on tumor necrosis factor receptor 1 (TNFR1). Inspired by these findings, we aimed to evaluate whether TNFR1 determine the therapeutic effects of hUC-MSCs on RA. First, we investigated whether TNFR1 is necessary for hUC-MSCs to inhibit TNF-α production of PBMCs, a source of elevated TNF-α in patients. Through coculture experiment, we confirmed that this inhibition was dependent on TNFR1. Subsequently, we administered hUC-MSCs or siTNFR1-MSCs to DBA/1J male mice with collagen-induced arthritis. The results indicated that hUC-MSCs significantly alleviated the pathological features of RA and suppressed the inflammatory cytokines IFN-γ, TNF-α, and IL-6 in peripheral blood, also in a manner dependent on TNFR1 either. Given the dramatic pathologic differences between hUC-MSCs and siTNFR1-MSCs treatments, we questioned whether production of growth factors and chemokines was significantly influenced by TNFR1. Consequently, we stimulated hUC-MSCs or siTNFR1-MSCs through IFN-γ, TNF-α, and IL-6, and profiled growth factors and chemokines in serum, which revealed significant changes of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), as well as chemokines CXCL9, CXCL10, IL-8, and RANTES. In summary, our findings suggest that TNFR1 may determine whether hUC-MSCs will gain abilities of anti-inflammation and tissue regeneration.https://doi.org/10.1177/09636897241301703 |
| spellingShingle | Guangyang Liu Herui Wang Chenliang Zhang Xin Li Yi Mi Yaoyao Chen Liqiang Xu Li Miao Haomiao Long Yongjun Liu Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy Cell Transplantation |
| title | Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy |
| title_full | Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy |
| title_fullStr | Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy |
| title_full_unstemmed | Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy |
| title_short | Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord–Derived Mesenchymal Stem Cell–Mediated Rheumatoid Arthritis Therapy |
| title_sort | tumor necrosis factor receptor 1 is required for human umbilical cord derived mesenchymal stem cell mediated rheumatoid arthritis therapy |
| url | https://doi.org/10.1177/09636897241301703 |
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