CD73 mediated host purinergic metabolism in intestine contributes to the therapeutic efficacy of a novel mesenchymal-like endometrial regenerative cells against experimental colitis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background The disruption of intestinal barrier functions and the dysregulation of mucosal immune responses, mediated by aberrant purinergic metabolism, are involved in the pathogenesis of inflammatory bowel diseases (IBD). A novel mesenchymal-like endometrial regenerative cells (ERCs) has demonstrated a significant therapeutic effect on colitis. As a phenotypic marker of ERCs, CD73 has been largely neglected for its immunosuppressive function in regulating purinergic metabolism. Here, we have investigated whether CD73 expression on ERCs is a potential molecular exerting its therapeutic effect against colitis. Methods ERCs either unmodified or with CD73 knockout (CD73 -/- ERCs), were intraperitoneally administered to dextran sulfate sodium (DSS)-induced colitis mice. Histopathological analysis, colon barrier function, the proportion of T cells, and maturation of dendritic cells (DCs) were investigated. The immunomodulatory effect of CD73-expressing ERCs was evaluated by co-culture with bone marrow-derived DCs under LPS stimulation. FACS determined DCs maturation. The function of DCs was detected by ELISA and CD4 + cell proliferation assays. Furthermore, the role of the STAT3 pathway in CD73-expressing ERCs-induced DC inhibition was also elucidated. Results Compared with untreated and CD73 -/- ERCs-treated groups, CD73-expressing ERCs effectively attenuated body weight loss, blo

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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