Bone-derived MSCs encapsulated in alginate hydrogel prevent collagen-induced arthritis in mice through the activation of adenosine A_(2A/2B)receptors in tolerogenic dendritic cells  

作　　者：Gaona Shi Yu Zhou Wenshuai Liu Chengjuan Chen Yazi Wei Xinlong Yan Lei Wu Weiwei Wang Lan Sun Tiantai Zhang 

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China [2]Tianjin Key Laboratory of Biomaterial Research,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300192,China [3]Faculty of Environmental and Life Sciences,Beijing University of Technology,Beijing 100124,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第6期2778-2794,共17页药学学报（英文版）

基　　金：supported by the National Key R&D Program of China(No.2020YFA0908004);the National Natural Science Foundation of China(Nos.82293684,82293680,82273936,82273929);CAMS Innovation Fund for Medical Science(No.2021-I2M-1-028,2022-I2M-2-002,2022-I2M-1-014,China);Natural Science Fund for Distinguished Young Scholars of Tianjin(No.21JCJQJC00020,China)。

摘　　要：Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

关 键 词：Mesenchymal stem cells Alginate hydrogel Tolerogenic dendritic cells IMMUNOTOLERANCE Adenosine A_(2A/2B)receptor CD39/CD73 Treg Rheumatoid arthritis 

分 类 号：R684.3[医药卫生—骨科学]