{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:38:26Z","timestamp":1776292706466,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea(NRF) grant","award":["2017R1C1B5015547"],"award-info":[{"award-number":["2017R1C1B5015547"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","award":["2019R1F1A1060787"],"award-info":[{"award-number":["2019R1F1A1060787"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-\u03b3) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt\/\u03b2-catenin pathway, JAK\/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-\u03b3-induced expression\u2014including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1\u03b2, and IL-15\u2014and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt\/\u03b2-catenin signaling pathway, such as in the Wnt families, \u03b2-catenin, phosphorylated GSK-3\u03b2 and cyclin D1, and suppressed the expression of DKK1 induced by IFN-\u03b3 in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-\u03b3-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt\/\u03b2-catenin and JAK\/STAT pathways in hORSCs.<\/jats:p>","DOI":"10.3390\/ijms22094581","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T21:18:20Z","timestamp":1619558300000},"page":"4581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt\/\u03b2-Catenin and JAK\/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-5586","authenticated-orcid":false,"given":"Yu-Jin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dermatology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song-Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7342-2808","authenticated-orcid":false,"given":"Hye-Ree","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-4760","authenticated-orcid":false,"given":"Hoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-0995","authenticated-orcid":false,"given":"Jung-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1056\/NEJMra1103442","article-title":"Alopecia Areata","volume":"366","author":"Gilhar","year":"2012","journal-title":"N. 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