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The development of regenerative therapies would revolutionize the treatment of endocrine disorders. As is the case for harvested organs, the ideal bioengineered graft would comprise vascularized endocrine tissue, contain blood vessels that could be anastomosed to host vessels, have stable blood flow, and be suitable for transplantation into various sites. Here, we describe a transplantable endocrine tissue graft that was fabricated by <jats:italic>ex vivo<\/jats:italic> perfusion of tricultured cell sheets (islet <jats:italic>\u03b2<\/jats:italic>-cells, vascular endothelial cells (vECs), and mesenchymal stem cells (MSCs)) on a vascularized tissue flap of <jats:italic>in vivo<\/jats:italic> origin. The present study has three key findings. First, mild hypothermic conditions enhanced the success of <jats:italic>ex vivo<\/jats:italic> perfusion culture. Specifically, graft construction failed at 37 \u00b0C but succeeded at 32 \u00b0C (mild hypothermia), and endocrine tissue fabricated under mild hypothermia contained aggregations of islet <jats:italic>\u03b2<\/jats:italic>-cells surrounded by dense vascular networks. Second, the construction of transplantable endocrine tissue by <jats:italic>ex vivo<\/jats:italic> perfusion culture was better achieved using a vascular flap (VF) than a muscle flap. Third, the endocrine tissue construct generated using a VF could be transplanted into the rat by anastomosis of the graft artery and vein to host blood vessels, and the graft secreted insulin into the host\u2019s circulatory system for at least two weeks after transplantation. Endocrine tissues bioengineered using these techniques potentially could be used as novel endocrine therapies.<\/jats:p>","DOI":"10.1088\/1758-5090\/ace9fc","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T22:28:44Z","timestamp":1690237724000},"page":"045010","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The bioengineering of perfusable endocrine tissue with anastomosable blood vessels"],"prefix":"10.1088","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-5575","authenticated-orcid":true,"given":"Hiroki","family":"Yago","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1976-0670","authenticated-orcid":false,"given":"Jun","family":"Homma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-5554","authenticated-orcid":false,"given":"Hidekazu","family":"Sekine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4387-4473","authenticated-orcid":false,"given":"Yuhei","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-4239","authenticated-orcid":true,"given":"Tatsuya","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"bface9fcbib1","doi-asserted-by":"publisher","first-page":"S145","DOI":"10.1161\/CIRCULATIONAHA.107.757286","article-title":"Endothelial cell coculture within tissue-engineered cardiomyocyte sheets enhances neovascularization and improves cardiac function of ischemic hearts","volume":"118","author":"Sekine","year":"2008","journal-title":"Circulation"},{"key":"bface9fcbib2","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1089\/ten.tea.2018.0030","article-title":"Mesenchymal stem cell sheets exert antistenotic effects in a rat arterial injury model","volume":"24","author":"Homma","year":"2018","journal-title":"Tissue Eng. 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