{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T18:37:21Z","timestamp":1769452641858,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1100500"],"award-info":[{"award-number":["2021YFA1100500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Recurrent pregnancy loss (RPL), defined as more than two consecutive miscarriages before 20 weeks of gestation, affects 1%\u20135% of reproductive\u2010aged women, with nearly half of the cases remaining idiopathic. Using ethanol\u2010induced endometrial injury in rats to simulate RPL, we demonstrated that mesenchymal stem cells (MSCs) exert therapeutic effects through two complementary mechanisms: CCR7\u2010mediated endometrial repair and immunomodulation of uterine natural killer (uNK) cells, compared to ethanol\u2010induced injury, this treatment achieved a 190% increase in embryo retention (from 2.4 to 7 embryos). Transcriptomic analysis and Western blotting of MSC\u2010cocultured NK92 cells revealed significant CCR7 upregulation (1.75\u2010fold increase at the optimal dose of 2\u2009\u00d7\u200910\n                    <jats:sup>4<\/jats:sup>\n                    \u2009cells\/mL MSCs) and activation of NK differentiation pathways. This was corroborated by immunofluorescence showing enhanced CCR7\n                    <jats:sup>+<\/jats:sup>\n                    NK cell infiltration in MSC\u2010treated endometria. MSCs administration altered cytokine profiles by decreasing pro\u2010inflammatory mediators (IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2) and increasing anti\u2010inflammatory IL\u201010 levels simultaneously. Mechanistically, MSCs orchestrate endometrial repair through sequential events: induce the formation of a gradient of CCR7 expression on the endometrial layer and the surface of NK cells; followed by ERK\/JNK pathway activation, which promotes CCR7\n                    <jats:sup>+<\/jats:sup>\n                    \u2009uNK cell generation; and finally initiates endometrial proliferation with an increased proportion of Ki67\n                    <jats:sup>+<\/jats:sup>\n                    cells. Our integrated multi\u2010omics approach\u2014combining RNA\u2010Seq, protein analysis, and cytokine profiling\u2014establishes the CCR7\u2010ERK\/JNK axis as a promising therapeutic target, providing clinically relevant parameters for MSCs dosing and administration protocols in idiopathic RPL management.\n                  <\/jats:p>","DOI":"10.1155\/sci\/9963200","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T05:25:41Z","timestamp":1768627541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal Stem Cells Restore Endometrial Integrity and Sustain Pregnancy via CCR7\u2010ERK\/JNK Signaling Modulation"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0661-8843","authenticated-orcid":false,"given":"Yunguo","family":"Lei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8766-1876","authenticated-orcid":false,"given":"Juanmei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3961-5020","authenticated-orcid":false,"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9176-5063","authenticated-orcid":false,"given":"Yunjun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5018-1759","authenticated-orcid":false,"given":"Weihua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuequn","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1935-520X","authenticated-orcid":false,"given":"Qiang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0006-3568","authenticated-orcid":false,"given":"Jianmei","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.06.048"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69204-0"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmg013"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198807283190401"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.10.042"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmac006"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1452"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det339"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez194"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.167"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-03854-6"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead246"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2009.02.030"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.088591"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-2185"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-013-9430-y"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.15436\/2471-0598.17.022"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v45.1.07"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605698"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0811415"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-333682"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2674"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-015-0007-0"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.111991"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2019.115636"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200108)31:8<2403::AID-IMMU2403>3.0.CO;2-O"}],"container-title":["Stem 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