{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:37:44Z","timestamp":1776915464511,"version":"3.51.2"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:00:00Z","timestamp":1700870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean government","award":["RS-2023-00279247"],"award-info":[{"award-number":["RS-2023-00279247"]}]},{"name":"PLABiologics Co., Ltd.","award":["RS-2023-00279247"],"award-info":[{"award-number":["RS-2023-00279247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The vascular network contributes to the development of follicles. However, the therapeutic mechanism between vascular remodeling and ovarian functions is still unclear. Therefore, we demonstrated whether increased HGF by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in an ovariectomized rat model via vascular remodeling by Wnt signaling activation. We established a half-ovariectomized rat model in which damaged ovaries were induced by ovariectomy of half of each ovary, and PD-MSCs (5 \u00d7 105 cells) were transplanted by intravenous injection. Three weeks after transplantation, rats in all groups were sacrificed. We examined the secretion of HGF by PD-MSCs through culture medium. The vascular structure in injured ovarian tissues was restored to a greater extent in the PD-MSC transplantation (Tx) group than in the nontransplantation (NTx) group (* p &lt; 0.05). The expression of genes related to Wnt signaling (e.g., LRP6, GSK3\u03b2, \u03b2-catenin) was significantly increased in the Tx group compared to the NTx group (* p &lt; 0.05). However, the expression of genes related to vascular permeability (e.g., Asef, ERG3) was significantly decreased in the Tx group compared to the NTx group (* p &lt; 0.05). Follicular development was improved in the Tx group compared to the NTx group (* p &lt; 0.05). Furthermore, to evaluate vascular function, we cocultivated PD-MSCs after human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and we analyzed the vascular formation assay and dextran assay in HUVECs. Cocultivation of PD-MSCs with injured HUVECs enhanced vascular formation and decreased endothelial cell permeability (* p &lt; 0.05). Also, cocultivation of PD-MSCs with explanted ovarian tissues improved follicular maturation compared to cocultivation of the Wnt inhibitor-treated PD-MSCs with explanted ovarian tissues. Therefore, HGF secreted by PD-MSCs improved ovarian function in rats with ovarian dysfunction by decreasing vascular permeability via Wnt signaling.<\/jats:p>","DOI":"10.3390\/cells12232708","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:33:56Z","timestamp":1701056036000},"page":"2708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Increased Hepatocyte Growth Factor Secretion by Placenta-Derived Mesenchymal Stem Cells Improves Ovarian Function in an Ovariectomized Rat Model via Vascular Remodeling by Wnt Signaling Activation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-5313","authenticated-orcid":false,"given":"Hyeri","family":"Park","sequence":"first","affiliation":[{"name":"Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"},{"name":"PLABiologics Co., Ltd., Seongnam-si 13522, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-5029","authenticated-orcid":false,"given":"Dae Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"},{"name":"PLABiologics Co., Ltd., Seongnam-si 13522, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-6077","authenticated-orcid":false,"given":"Jun Hyeong","family":"You","sequence":"additional","affiliation":[{"name":"Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5805-3736","authenticated-orcid":false,"given":"Jin","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja-Yun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Science, Hyejeon College, Hongsung-gun 32244, Chungnam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2320-7157","authenticated-orcid":false,"given":"Gi Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioinspired Science, CHA University, Seongnam-si 13488, Gyeonggi-do, Republic of Korea"},{"name":"PLABiologics Co., Ltd., Seongnam-si 13522, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,25]]},"reference":[{"key":"ref_1","first-page":"111","article-title":"Role of vascular endothelial growth factor in ovarian physiology\u2014An overview","volume":"5","author":"Kaczmarek","year":"2005","journal-title":"Reprod. 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