{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T23:13:44Z","timestamp":1778022824967,"version":"3.51.4"},"reference-count":101,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009408","name":"Brain Canada Foundation","doi-asserted-by":"publisher","award":["The W. Garfield Weston Foundation"],"award-info":[{"award-number":["The W. Garfield Weston Foundation"]}],"id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-\u00b5Ts) that are suitable for scalable production and delivery via injection. RPE-\u00b5Ts retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch\u2019s membrane, suggesting that RPE-\u00b5Ts may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery.<\/jats:p>","DOI":"10.3390\/ijms222111317","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T07:05:57Z","timestamp":1634713557000},"page":"11317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-7033","authenticated-orcid":false,"given":"Abdullah","family":"Al-Ani","sequence":"first","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5114-7147","authenticated-orcid":false,"given":"Derek","family":"Toms","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saud","family":"Sunba","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla","family":"Giles","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yacine","family":"Touahri","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3567-0058","authenticated-orcid":false,"given":"Carol","family":"Schuurmans","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-1491","authenticated-orcid":false,"given":"Mark","family":"Ungrin","sequence":"additional","affiliation":[{"name":"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rakoczy, E.P. 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