Abstract Background Intrauterine adhesion (IUA) is a common gynecological disease that contributes to infertility. Decreased endometrial angiogenesis and uterine ischemia are major therapeutic challenges for IUA and cannot be addressed by current treatment strategies. Human endometrial mesenchymal stem cells (H-EMSCs) and macrophages (mø) are both important cell types that reside within the endometrial tissue and participate in its repair and regeneration. However, how to harness the endometrial tissue repair potential of H-EMSCs and mø simultaneously in a co-delivery system and whether there are significant biochemical cross-talks between the two cell types so that they can regulate each other to specifically boost endometrial tissue angiogenesis remains to be explored. Methods This study developed a H-EMSCs-mø co-delivery system using an electrospun polycaprolactone-hyaluronic acid (PCL-HA) membrane and established a rat endometrial damage model. The effects of the co-delivery system on endometrial tissue repair (endometrium thickness, endometrial glands number) and angiogenesis were investigated. The mechanisms underlying the enhanced endometrial tissue angiogenesis of the H-EMSCs-mø co-delivery system were also delineated. All data were analyzed using analysis of variance with Tukey’s test for pair-wise comparisons or an independent samples t-test where appropriate. Results In this study, it was found that a H-EMSCs and mø co-delivery system developed with a PCL-HA electrospun membrane carrier (PCL-HA/H-E/mø) significantly increased the endometrium thickness and restored the number of endometrial glands at day 7 and 14 in the endometrial damage model vs. the NR (normal repair) and PCL-HA alone groups. Further, PCL-HA/H-E/mø enhanced more CD31 gene and protein expression, indicating great potential for angiogenesis to occur at day 7 and 14 post-implantation, when compared with PCL-HA/H-E, NR or PCL-HA alone. It was also proved to demonstrated that elevated VEGF production was one of the potential factors that contributed to the enhanced angiogenesis of the co-delivery patch system. Conclusions This study provided significant insights into the use of co-delivered H-EMSCs and mø, on a PCL-HA hybrid electrospun membrane, for effectively inducing endometrial angiogenesis and repair to enhance IUA treatment outcomes.
An et al. (Mon,) studied this question.