Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis

• DOI: 10.1186/s13287-024-03764-7
• Publication Date: 2024-05-23T23:02:48Z
• Authors: Yanan Duan; Xiteng Chen; Hui Shao; Yongtao Li; Zhihui Zhang; Huan Li; Chuan Zhao; Hong Xiao; Jiawei Wang; Xiaomin Zhang
• Keywords: Regenerative Medicine

Abstract Background Autoimmune uveitis is an inflammatory disease triggered by aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, ectoenzyme present on MSC-sEVs, involved in mitigating inflammation converting adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs experimental autoimmune (EAU) could be partially attributed to surface expression CD73. Methods To investigate novel approaches uveitis, we performed lentiviral transduction overexpress CD73 yielding CD73-enriched (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated 50 µg vector infected sEVs-CD73 or PBS via single tail vein injection. evaluated clinical histological features induced mice analyzed proportion functional capabilities T helper cells. Furthermore, T-cells co-cultured various vitro, quantified resulting response assess benefits sEVs-CD73. Results Compared significantly alleviates EAU, leading reduced diminished tissue damage. Treatment results a decreased Th1 cells spleen, draining lymph nodes, eyes, accompanied increased regulatory (Treg cells). In vitro assays further reveal inhibits T-cell proliferation, suppresses differentiation, enhances Treg proportion. Conclusion Over-expression their immunosuppressive effects indicating has efficient immunotherapeutic agent uveitis.