Effects of treatment with stem cell-derived extracellular vesicles in preclinical rodent models of intrauterine adhesion: A meta-analysis

Abstract

Background: Intrauterine adhesion (IUA) results from serious complications of intrauterine surgery or infection and mostly remains incurable. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have emerged as a potential new approach for the treatment of IUA; however, their impact is not fully understood. Here, we performed a meta-analysis summarizing the effects of sEVs on IUA in preclinical rodent models. Methods: This meta-analysis included searches of PubMed, EMBASE, Cochrane, and the Web of Science databases from January 1, 1997, to April 1, 2022, to identify studies reporting the therapeutic effect of sEVs on rodent preclinical animal models of IUA. We compared improvements in endometrial thickness, endometrial gland number, fibrosis area, embryo number, vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGFβ1), and leukemia inhibitory factor (LIF) levels after treatment. Results: Our search included 100 citations, of which 7 met the inclusion criteria, representing 231 animals. Compared with that in the control group, the fibrosis area in the sEV-treated group was significantly reduced (standardized mean difference (SMD) = −6.87，95 % confidence interval (CI) = −9.67 to −4.07). The number of glands increased after the intervention (95 % CI, 3.72–7.68; P = 0.000). Endometrial thickness was significantly improved in the sEV-treated group (SMD = 2.57, 95 % CI, 1.62–3.52). Conclusions: This meta-analysis is highlighting that sEV treatment can improve the area of endometrial fibrosis, as well as VEGF, and LIF level, in a mouse IUA model. This knowledge of these findings will provide new insights into future preclinical research.

Keywords

• Intrauterine adhesion
• Stem cell
• Small extracellular vesicles
• Meta-analysis
• Animal models