{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:26:10Z","timestamp":1785763570360,"version":"3.56.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771993"],"award-info":[{"award-number":["81771993"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research","award":["2019CXJQ01"],"award-info":[{"award-number":["2019CXJQ01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Most perimenopausal and postmenopausal women experience estrogen deficiency\u2013induced vaginal atrophy. However, estrogen replacement therapy has contraindications and side effects, which makes it unsuitable for most women. Cell-free fat extract (CEFFE) has pro-proliferative and proangiogenic tissue regeneration activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The purpose of this study was to evaluate the effect of topical application of CEFFE in the vagina and the effect of CEFFE on vaginal keratinocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ovariectomized mice were treated with CEFFE via vaginal topical application for 2 weeks. The vaginal mucosal cell layer number, mucosal thickness, and vaginal collagen volume were determined by histologic analyses. Vaginal mucosa proliferation and lamina propria angiogenesis were evaluated with anti\u2013proliferating cell nuclear antigen and anti-CD31 staining, respectively. For in vitro analysis, VK2\/E6E7 cells were administered, increasing the CEFFE concentration. Cell proliferation and cell-cycle distribution were analyzed by Cell Counting Kit 8 assay and flow cytometry, respectively. Mucosal migration was evaluated with a wound-healing assay. The expression of Ki-67 and estrogen-related proteins was detected by western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CEFFE-treated mice showed increased mucosal thickness and number of vaginal mucosal cell layers and reduced vaginal atrophy compared to ovariectomized mice. The number of proliferating cell nuclear antigen\u2013positive cells and CD31-positive capillaries also increased. In addition, CEFFE promoted the proliferation and migration of VK2\/E6E7 cells, upregulated the expression of Ki-67, and inhibited the expression of estrogen-related proteins and the PI3K\/AKT pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CEFFE prevents estrogen deficiency\u2013induced vaginal atrophy by promoting vaginal mucosal proliferation and increasing neovascularization, but not through the estrogen\/estrogen receptor pathway, in an ovariectomized mouse model.<\/jats:p><\/jats:sec>","DOI":"10.1093\/asj\/sjab366","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:34:40Z","timestamp":1634769280000},"page":"NP55-NP68","source":"Crossref","is-referenced-by-count":11,"title":["Cell-Free Fat Extract Prevents Vaginal Atrophy in an Ovariectomized Model by Promoting Proliferation of Vaginal Keratinocytes and Neovascularization"],"prefix":"10.1093","volume":"42","author":[{"given":"Bijun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai 9th People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizuo","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai 9th People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai 9th People\u2019s Hospital, 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