{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:39:12Z","timestamp":1790163552809,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T00:00:00Z","timestamp":1369353600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T00:00:00Z","timestamp":1369353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Human hematopoietic stem cells (HSCs) have been clinically used for transplantation and gene and cellular therapy for more than 4 decades. However, this use is limited because of the challenges in the <jats:italic>ex vivo<\/jats:italic> culturing of HSCs. The major hurdle is to amplify these cells without losing their self-renewing property.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>In our study, we tested 3\u2032,4\u2032-dimethoxyflavone (3\u20324\u2032-DMF) and valproic acid (VPA) on the <jats:italic>ex vivo<\/jats:italic> expansion of HSCs under both normoxic (20% O<jats:sub>2<\/jats:sub>) and hypoxic (1% O<jats:sub>2<\/jats:sub>) conditions. 3\u20324\u2032-DMF is a widely used anticancer drug that acts as a competitive antagonist of the aryl hydrocarbon receptor. VPA is a potent inhibitor of histone deacetylase and is used in the treatment of neurologic disorders.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Culturing HSCs (from mobilized peripheral blood) under normoxia, with 3\u20324\u2032-DMF and VPA, highly preserved the CD34 positivity (3\u20324\u2032-DMF, 22.1%, VPA, 20.3%) after 1 week and strongly enhanced the CD34<jats:sup>+<\/jats:sup> cells (3\u20324\u2032-DMF, 27.8 fold; VPA, 34.1 fold) compared with the control cultures (11.6% and 14.4 fold). Addition of 3\u20324\u2032-DMF and VPA also resulted in more primary colonies and replating efficiency compared with control cultures. Although no significant effect was observed on the enhancement of CD34<jats:sup>+<\/jats:sup> cells under hypoxia, the number of primary colonies was significantly higher than the control cultures.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Based on these findings, this study presents, for the first time, <jats:italic>in vitro<\/jats:italic> evidence for a new and relevant effect of 3\u20324\u2032-DMF on human HSCs. In addition, the results suggest a potential clinical use of 3\u20324\u2032-DMF and VPA in HSC therapy.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/scrt208","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T12:14:57Z","timestamp":1369397697000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["3\u2032,4\u2032-Dimethoxyflavone and valproic acid promotes the proliferation of human hematopoietic stem cells"],"prefix":"10.1186","volume":"4","author":[{"given":"Kiranpreet","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Mirlashari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Kvalheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kjeldsen-Kragh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,5,24]]},"reference":[{"key":"208_CR1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/toxsci\/58.2.235","volume":"58","author":"JE Lee","year":"2000","unstructured":"Lee JE, Safe S: 3\u2032,4\u2032-Dimethoxyflavone as an aryl hydrocarbon receptor antagonist in human breast cancer cells. 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