M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

M1 巨噬细胞衍生的纳米囊泡使 M2 巨噬细胞重新极化,从而抑制子宫内膜异位症的发展

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作者:Qiuju Li, Ming Yuan, Xue Jiao, Yufei Huang, Jing Li, Dong Li, Miaomiao Ji, Guoyun Wang

Background

Endometriosis is a common nonmalignant gynecological disorder that affects 10-15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis.

Conclusions

M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.

Methods

M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis.

Results

M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs. Conclusions: M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.

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