{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:01:12Z","timestamp":1790827272969,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2019,8]]},"abstract":"Abstract<\/jats:title>Purpose<\/jats:title>To study immunogenic properties of human embryonic stem cell\u2013derived retinal pigment epithelium (hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content>) and to evaluate subretinal xenotransplantation of hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> on porous polyethylene terephthalate (PET<\/jats:styled-content>) in rabbits.<\/jats:p><\/jats:sec>Methods<\/jats:title>Human ESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> cells were characterized by morphology, transepithelial electrical resistance (TER<\/jats:styled-content>), protein expression and photoreceptor outer segment phagocytosis in\u00a0vitro<\/jats:italic>. Expression of major histocompatibility complex (MHC<\/jats:styled-content>) proteins was assessed in conventionally or xeno\u2010free produced hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content>\u00a0\u00b1\u00a0interferon\u2010gamma (IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic>) stimulation (n<\/jats:italic>\u00a0=\u00a01). Xeno\u2010free hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> on PET<\/jats:styled-content> with TER<\/jats:styled-content>\u00a0<\u00a0200\u00a0\u03a9\u00b7cm2\u00a0<\/jats:sup>>\u00a0or PET<\/jats:styled-content> alone were transplanted into 18 rabbits with short\u2010term triamcinolone\u00a0\u00b1\u00a0extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4\u00a0weeks, the eyes were processed for histology and transmission electron microscopy.<\/jats:p><\/jats:sec>Results<\/jats:title>Upon in\u00a0vitro <\/jats:italic>IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> stimulation, xeno\u2010free hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> expressed lower level of MHC<\/jats:styled-content>\u2010II<\/jats:styled-content> proteins compared to the conventional cells. Outer nuclear layer (ONL<\/jats:styled-content>) atrophy was observed over the graft in most cases 4\u00a0weeks post\u2010transplantation. In 3\/4 animals with high TER hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content>, but only in 1\/3 animals with low TER hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content>, ONL<\/jats:styled-content> atrophy was observed already within 1\u00a0week. Retinal cell infiltrations were more frequent in animals with high TER hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content>. However, the difference was not statistically significant. In three animals, preservation of ONL<\/jats:styled-content> was observed. Weekly intravitreal tacrolimus did not affect ONL<\/jats:styled-content> preservation. In all animals, hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> cells survived for 4\u00a0weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC<\/jats:styled-content>\u2010RPE (n<\/jats:italic>\u00a0=\u00a01).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Xenografted xeno\u2010free hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> monolayers can survive and retain some functionality for 4\u00a0weeks following short\u2010term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> xenografts in rabbits should be addressed especially toward the roles of hESC<\/jats:styled-content>\u2010RPE<\/jats:styled-content> maturation stage and extended intravitreal immunosuppression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.14004","type":"journal-article","created":{"date-parts":[[2018,12,29]],"date-time":"2018-12-29T04:59:51Z","timestamp":1546059591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Survival and functionality of xeno\u2010free human embryonic stem cell\u2013derived retinal pigment epithelial cells on polyester substrate after transplantation in rabbits"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-8897","authenticated-orcid":false,"given":"Tanja","family":"Ilmarinen","sequence":"first","affiliation":[{"name":"BioMediTech Institute Faculty of Medicine and Life Sciences University of Tampere Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Thieltges","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Hongisto","sequence":"additional","affiliation":[{"name":"BioMediTech Institute Faculty of Medicine and Life Sciences University of Tampere Tampere Finland"},{"name":"Department of Ophthalmology Institute of Clinical Medicine University of Eastern Finland Kuopio 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