{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:59:56Z","timestamp":1778180396873,"version":"3.51.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Research funding provided by Mitsubishi Chemical Corporation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Bioactive cytokines such as vascular endothelial growth factor (VEGF) and Activin A are critical for the differentiation of stem cells into vascular endothelial cells and cardiomyocytes. However, production of the cytokines using conventional <jats:italic>Escherichia coli<\/jats:italic> or mammalian cell expression systems carries risks of immunogenicity and viral contamination. In this study, we developed a VEGF and Activin A plant expression system and demonstrated that plant-expressed VEGF and Activin A are as active as their commercial counterparts. We also showed that plant-expressed VEGF and Activin A are as efficient as human recombinant counterparts in inducing endothelial cells and cardiomyocytes from human pluripotent stem cells. These results suggest that plant-expressed VEGF and Activin A are promising alternatives for the safe and efficient production of cardiac cells, specifically cardiomyocytes and endothelial cells, for stem cell-based regenerative medicine.<\/jats:p>","DOI":"10.1186\/s13287-025-04424-0","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T23:01:28Z","timestamp":1750806088000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Production of bioactive cytokines using plant expression system for cardiovascular cell differentiation from human pluripotent stem cells"],"prefix":"10.1186","volume":"16","author":[{"given":"Kozue","family":"Murata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanae","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akitomo","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiteru","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4059-2827","authenticated-orcid":false,"given":"Hidetoshi","family":"Masumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"4424_CR1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.semcdb.2014.05.017","volume":"32","author":"F Itoh","year":"2014","unstructured":"Itoh F, Watabe T, Miyazono K. Roles of TGF-\u03b2 family signals in the fate determination of pluripotent stem cells. Semin Cell Dev Biol. 2014;32:98\u2013106. https:\/\/doi.org\/10.1016\/j.semcdb.2014.05.017.","journal-title":"Semin Cell Dev Biol"},{"key":"4424_CR2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.lfs.2018.01.009","volume":"196","author":"ME Yassa","year":"2018","unstructured":"Yassa ME, Mansour IA, Sewelam NI, Hamza H, Gaafar T. The impact of growth factors on human induced pluripotent stem cells differentiation into cardiomyocytes. Life Sci. 2018;196:38\u201347. https:\/\/doi.org\/10.1016\/j.lfs.2018.01.009.","journal-title":"Life Sci"},{"key":"4424_CR3","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1073\/pnas.032074999","volume":"99","author":"S Levenberg","year":"2002","unstructured":"Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R. Endothelial cells derived from human embryonic stem cells. 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For their use in this research, the providing institution did not require approval from the ethics committee of the using institution (Research Ethics Committee 1 of RIKEN Kobe Branch).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This work was supported by research funding and reagents provided by Mitsubishi Chemical Corporation. Co-authors Watanabe, Nagashima, Miyauchi and Miyauchi are employees of Mitsubishi Chemical Corporation and were involved in study design. However, they did not participate in data collection and interpretation for the key experiments differentiating cardiovascular cells from stem cells, nor in drafting the manuscript section describing those experiments.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"303"}}