Exosomes From Adipose-Derived Stem Cells Suppress the Progression of Chronic Endometritis

Abstract

Chronic endometritis (CE) is closely linked to the reproductive failure. Exosome (Exo)-based therapy is proposed as an encouraging strategy in inflammation-related disorders; however, little work has been devoted to its usage in CE therapy. An in vitro CE was established by administration of lipopolysaccharide (LPS) in human endometrial stromal cells (HESCs). The cell proliferation, cell apoptosis, and inflammatory cytokine assays were performed in vitro, and the efficacy of Exos derived from adipose tissue–derived stem cells (ADSCs) was evaluated in a mouse model of CE. We found that Exos isolated from ADSCs could be taken up by HESCs. Exos elevated the proliferation and inhibited apoptosis in LPS-treated HESCs. Administration of Exos to HESCs suppressed the content of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Moreover, Exos exposure repressed the inflammation stimulated by LPS in vivo. Mechanistically, we demonstrated that Exos exerted their ant-inflammatory effect via miR-21/TLR4/NF-kB signaling pathway in endometrial cells. Our findings suggest that ADSC-Exo-based therapy might serve as an attractive strategy for the treatment of CE.

Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases

“…However, IFN-γ suppressed miR-221 [117]. In addition, exosomes enriched in miR-21 exerted an anti-inflammatory effect by blocking TLR4 and NF-kB signaling pathways [118]. However, miR-21 was downregulated by high glucose in diabetic patients [119].…”

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

“…Research has shown that miR-21 expression is considerably downregulated following an LPS challenge, suggesting that miR-21 is involved in the endometrial inflammatory response ( Ibrahim et al., 2019 ). In recent study, it was also shown that exposure to LPS decreased miR-21 levels in hESCs, while administration of AD-MSCs-derived exosomes resulted in increased miR-21 expression ( Wang et al., 2023 ). Based on reports, overexpression of miR-21 inactivates TLR4/NF-kB pathway by downregulation of TLR4 expression ( Liu X-J.…”

“…Also, a study performed by Wang et al. showed that exosomes from AD-MSCs can suppress the progression of chronic endometritis (CE) ( Wang et al., 2023 ). For this purpose, human endometrial stromal cells (hESCs) were used to create an in vitro CE and a mouse model with LPS-induced CE in vivo was used to assess the effectiveness of Exos derived from AD-MSCs in vivo ( Wang et al., 2023 ).…”

“…Furthermore, exposure to AD-MSCs-derived exosomes suppressed LPS-stimulated inflammation in vivo. In addition, evaluations showed that endometrial cells, the miR-21/TLR4/NF-kB signaling pathway is how exosome reduce inflammation ( Wang et al., 2023 ). Research has shown that miR-21 expression is considerably downregulated following an LPS challenge, suggesting that miR-21 is involved in the endometrial inflammatory response ( Ibrahim et al., 2019 ).…”

“…Also, a study performed by Wang et al showed that exosomes from AD-MSCs can suppress the progression of chronic endometritis (CE) (Wang et al, 2023). For this purpose, human endometrial stromal cells (hESCs) were used to create an in vitro CE and a mouse model with LPS-induced CE in vivo was used to assess the effectiveness of Exos derived from AD-MSCs in vivo (Wang et al, 2023). Generally, CE is an infectious and inflammatory disease associated with long-term, continuous and mild inflammation of the endometrium, which defined by the endometrium's stromal area becoming infiltrated by plasma cells (Puente et al, 2020).…”