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However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn<jats:sup>2+<\/jats:sup>) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4\/4,100%) after transplantation of 96 3D-cultured IPCs. Zn<jats:sup>2+<\/jats:sup> concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. 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Pancreas. 36, 417\u2013423 (2008).","journal-title":"Pancreas."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55172-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55172-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55172-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T17:06:51Z","timestamp":1671296811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55172-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,10]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["55172"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-55172-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,10]]},"assertion":[{"value":"18 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Ikemoto and Dr. Shimada were funded by the Regenerative Medicine Cooperative of Fujifilm Corporation and Tokushima University. Dr. Ikemoto, Dr. Yamada, Dr. Saito, Dr. Morine, and Dr. Imura were also funded in part by grants-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (grant no. 16K10429). Dr. Ikemoto and Dr. Shimada were also funded in part by a grant from the Japan IDDM network. Dr. Ohta and Dr. Wada declare no potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18731"}}