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Survival and functionality of xeno‐free human embryonic stem cell–derived retinal pigment epithelial cells on polyester substrate after transplantation in rabbits
Author(s) -
Ilmarinen Tanja,
Thieltges Fabian,
Hongisto Heidi,
JuutiUusitalo Kati,
Koistinen Arto,
Kaarniranta Kai,
Brinken Ralf,
Braun Norbert,
Holz Frank G.,
Skottman Heli,
Stanzel Boris V.
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.14004
Subject(s) - embryonic stem cell , transplantation , polyester , stem cell , substrate (aquarium) , retinal , pigment , microbiology and biotechnology , chemistry , biology , ophthalmology , medicine , surgery , biochemistry , organic chemistry , gene , ecology
Abstract Purpose To study immunogenic properties of human embryonic stem cell–derived retinal pigment epithelium ( hESC ‐ RPE ) and to evaluate subretinal xenotransplantation of hESC ‐ RPE on porous polyethylene terephthalate ( PET ) in rabbits. Methods Human ESC ‐ RPE cells were characterized by morphology, transepithelial electrical resistance ( TER ), protein expression and photoreceptor outer segment phagocytosis in vitro . Expression of major histocompatibility complex ( MHC ) proteins was assessed in conventionally or xeno‐free produced hESC ‐ RPE ± interferon‐gamma ( IFN ‐ γ ) stimulation ( n = 1). Xeno‐free hESC ‐ RPE on PET with TER < 200 Ω·cm 2 > or PET alone were transplanted into 18 rabbits with short‐term triamcinolone ± extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4 weeks, the eyes were processed for histology and transmission electron microscopy. Results Upon in vitro IFN ‐ γ stimulation, xeno‐free hESC ‐ RPE expressed lower level of MHC ‐ II proteins compared to the conventional cells. Outer nuclear layer ( ONL ) atrophy was observed over the graft in most cases 4 weeks post‐transplantation. In 3/4 animals with high TER hESC ‐ RPE , but only in 1/3 animals with low TER hESC ‐ RPE , ONL atrophy was observed already within 1 week. Retinal cell infiltrations were more frequent in animals with high TER hESC ‐ RPE . However, the difference was not statistically significant. In three animals, preservation of ONL was observed. Weekly intravitreal tacrolimus did not affect ONL preservation. In all animals, hESC ‐ RPE cells survived for 4 weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC ‐RPE ( n = 1). Conclusions Xenografted xeno‐free hESC ‐ RPE monolayers can survive and retain some functionality for 4 weeks following short‐term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC ‐ RPE xenografts in rabbits should be addressed especially toward the roles of hESC ‐ RPE maturation stage and extended intravitreal immunosuppression.