{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:00:58Z","timestamp":1793635258686,"version":"4.5.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"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. Bioeng. Biotechnol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Thin endometrial tissue is a leading cause of embryo transfer failure, potentially contributing to sustained infertility and associated adverse outcomes. The application of exosomes derived from autologous or allogeneic bone marrow-derived stem cells (BMSCs) has been used to promote uterine repair following injury, and there is also prior evidence that stem cell transplantation can bolster fertility. Genetic modifications represent a primary approach to enhancing exosomal therapy strategies. The present study thus explored the effects of Cardiotrophin-1 (CTF1)-modified BMSCs-exo on fertility-related outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> An adenoviral vector was used to generate CTF1-overexpressing BMSCs (C-BMSCs), after which exosomes were isolated from control BMSCs (BMSC-exos) and C-BMSCs (C-BMSC-exos). The angiogenic effects of C-BMSC-exo treatment were assessed through analyses of endothelial cell proliferation and tube formation. Model rats exhibiting endometrial thinning were administered C-BMSCs-exo, after which the effects of such treatment were assessed through H&amp;amp;E staining, Masson\u2019s trichrome staining, and immunofluorescence analyses. The mechanistic basis for the proangiogenic effects of CTF1 as a driver of endometrial regeneration was additionally explored.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> C-BMSC-exo treatment of HUVECs was associated with enhanced neovascularization, as evidenced by improved <jats:italic>in vitro<\/jats:italic> proliferation, migration, and tube formation. Importantly, such treatment was also linked to tissue regeneration, neovascularization, and the suppression of localized tissue fibrosis <jats:italic>in vivo<\/jats:italic>. Regenerated endometrial tissue exhibited higher embryo receptivity and was associated with higher birth rates in treated rats. The upregulation of the JAK\/PI3K\/mTOR\/STAT3 signaling pathways in C-BMSC-exo-treated rats may underscore the mechanistic basis whereby CTF1 can positively impact endometrial angiogenesis and regeneration.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our data suggest that exosomes produced by CTF1-modified BMSCs can more effectively promote the regeneration of endometrial and myometrial tissues, driving neovascularization in a manner that improves endometrial receptivity in a rat model system, highlighting the therapeutic promise of this approach for patients diagnosed with endometrial thinning.<\/jats:p>","DOI":"10.3389\/fbioe.2022.868734","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T04:39:27Z","timestamp":1649824767000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Exosomes Derived From CTF1-Modified Bone Marrow Stem Cells Promote Endometrial Regeneration and Restore Fertility"],"prefix":"10.3389","volume":"10","author":[{"given":"Qianqian","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengluan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S0029-7844(99)00262-810.1097\/00006250-199907000-00031","article-title":"Angiogenesis of the Endometrium","volume":"94","author":"Abulafia","year":"1999","journal-title":"Obstet. 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