{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:17:26Z","timestamp":1761653846385,"version":"build-2065373602"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN\u2010148407"],"award-info":[{"award-number":["FDN\u2010148407"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004089","name":"Krembil Foundation","doi-asserted-by":"publisher","award":["410005024"],"award-info":[{"award-number":["410005024"]}],"id":[{"id":"10.13039\/501100004089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Blindness as a consequence of degenerative eye diseases (e.g., age\u2010related macular degeneration and retinitis pigmentosa) is a major health problem and numbers are expected to increase by up to 50% by 2020. Unfortunately, adult mouse and human retinal stem cells (RSCs), unlike fish and amphibians\n                    <jats:bold>,<\/jats:bold>\n                    are quiescent in vivo and do not regenerate following disease or injury. To replace lost cells, we used microcarriers (MCs) in a suspension stirring bioreactor to help achieve numbers suitable for differentiation and transplantation. We achieved a significant 10\u2010fold enrichment of RSC yield compared to conventional static culture techniques using a combination of FACTIII MCs and relative hypoxia (5%) inside the bioreactor. We found that hypoxia (5% O\n                    <jats:sub>2<\/jats:sub>\n                    ) was associated with better RSC expansion across all platforms; and this can be attributed to hypoxia\u2010induced increases in survival and\/or symmetric division of stem cells. In the future, we will target the differentiation of RSCs and their progeny toward rod and cone photoreceptor phenotypes using FACTIII MCs inside bioreactors to expand their populations in order to produce the large numbers of cells needed for transplantation.\n                  <\/jats:p>","DOI":"10.1002\/btpr.2800","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T13:08:22Z","timestamp":1551877702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expansion of retinal stem cells and their progeny using cell microcarriers in a bioreactor"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-1103","authenticated-orcid":false,"given":"Tahani","family":"Baakdhah","sequence":"first","affiliation":[{"name":"Institute of Medical Science University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"van der Kooy","sequence":"additional","affiliation":[{"name":"Institute of Medical Science University of Toronto  Toronto Ontario Canada"},{"name":"Department of Molecular Genetics University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5460.2032"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2473"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401596101"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1470"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(02)00400-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-4725.2003.690.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.2012027"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901596106"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.423"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.11.016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.279"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033338"},{"key":"e_1_2_8_14_1","first-page":"14","article-title":"Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non\u2010cell autonomous influences","author":"Del Debbio CB","year":"2013","journal-title":"BMC Neurosci"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1283"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1470"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2014.01.001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.10.008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.03.008"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevBiomedEng.v37.i4-5.30"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18681"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2361763"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000347"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173575"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.092270"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08123.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ie001107y"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.3233"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2007.05.034"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2009000600007"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.20900"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp050059f"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-010-0355-0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp050430z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260390308"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04537.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.01.086"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp060155w"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.73"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.224"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(19960620)50:6<627::AID-BIT3>3.0.CO;2-M"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.21191"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.591"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2008.07.1997"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1515"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0040"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00772197"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-007-9604-2"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v5.i4.124"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02348431"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0558"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21812"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3591"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027029"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608155103"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2011.0225"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.11.001"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1339"},{"key":"e_1_2_8_60_1","first-page":"1077","article-title":"Three\u2010dimensional retinal organoids from mouse pluripotent stem cells mimic in vivo development with enhanced stratification and rod photoreceptor differentiation","volume":"22","author":"Chen HY","year":"2016","journal-title":"Mol Vis"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.09.010"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118201"}],"container-title":["Biotechnology Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbtpr.2800","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.2800","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btpr.2800","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.2800","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:12:31Z","timestamp":1761653551000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btpr.2800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/btpr.2800"],"URL":"https:\/\/doi.org\/10.1002\/btpr.2800","archive":["Portico"],"relation":{},"ISSN":["8756-7938","1520-6033"],"issn-type":[{"type":"print","value":"8756-7938"},{"type":"electronic","value":"1520-6033"}],"subject":[],"published":{"date-parts":[[2019,3,28]]},"assertion":[{"value":"2018-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2800"}}