{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:41:49Z","timestamp":1789771309337,"version":"4.0.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Intrauterine adhesion (IUA) is characterized by endometrial fibrosis with partial or complete obliteration of the uterine cavity due to adhesion of the uterine wall. Currently, there is lack of effective strategies to address IUA and a strategy that can resolve endometrial fibrosis is needed. Human endometrial mesenchymal stem cells (H-EMSCs) and macrophages (m\u00f8) both reside in endometrial tissues and are important for endometrial repair. However, whether co-delivery of H-EMSCs and m\u00f8 using a biocompatible biomaterial platform could address endometrial fibrosis and enhance repair remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study developed a H-EMSCs-m\u00f8 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 fibrosis, M1 and M2 m\u00f8 phenotypic marker modulation, and the pro-inflammatory (TNF-\u03b1) and anti-inflammatory (IL-10) factor production were investigated. The mechanisms involved in the interactions between H-EMSCs and m\u00f8 were also delineated. All data were analyzed using analysis of variance with Tukey\u2019s test for pair-wise comparisons or an independent samples t-test where appropriate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the rat endometrial damage model, H-EMSCs and m\u00f8 co-delivery system (PCL-HA\/H-E\/m\u00f8) could significantly reduce endometrial fibrosis at day 14 after implantation vs. PCL-HA alone or H-EMSCs single-delivery (PCL-HA\/H-E). In addition, PCL-HA\/H-E\/m\u00f8 supported M1 (CD80, CD86) to M2-type m\u00f8 phenotypic marker change and enhanced MSC marker (CD90) expression at days 3, 7 and 14, when compared to PCL-HA and PCL-HA\/H-E groups. Moreover, PCL-HA\/H-E\/m\u00f8 system had lower TNF-\u03b1 gene expression but higher IL-10 gene and protein expression at day 7 post-implantation, suggesting an overall change from a more pro-inflammatory to a more wound-healing endometrial tissue microenvironment. In probing the mechanisms underlying the anti-fibrotic effect of the PCL-HA\/H-E\/m\u00f8 system, it was found that IL-10 could have significantly reduced endometrial tissue fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussions<\/jats:title>\n                    <jats:p>Co-delivery system reduced fibrosis and supported an M1-type to M2-type overall change of the m\u00f8 phenotypes in the endometrial tissue damage model. IL-10 was one of the important factors in inhibiting endometrial fibrosis in the co-delivery system. This study provided significant insights into using a co-delivery system PCL-HA\/H-E\/m\u00f8, to effectively alleviate endometrial fibrosis and potentially for a more effective treatment of IUA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1750456","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:23:35Z","timestamp":1771478615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Co-delivery of endometrial mesenchymal stem cells and macrophages with an electrospun patch suppresses endometrial fibrosis via IL-10 related signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiangru","family":"An","sequence":"first","affiliation":[{"name":"International Joint Laboratory of Biomaterials and Tissue Regeneration, School of Basic Medicine, Binzhou Medical University","place":["Yantai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Yuhuangding Hospital","place":["Yantai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Li Ka Shing Faculty of Medicine, The University of Hong Kong","place":["Pokfulam, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Yuhuangding Hospital","place":["Yantai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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