title: Ultrathin Polyimide Membrane as Cell Carrier for Subretinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigment Epithelium.
abstract: In this study, we investigated the suitability of ultrathin and porous polyimide (PI) membrane as a carrier for subretinal transplantation of human embryonic stem cell (hESC) -derived retinal pigment epithelial (RPE) cells in rabbits. The in vivo effects of hESC-RPE cells were analyzed by subretinal suspension injection into Royal College of Surgeons (RCS) rats. Rat eyes were analyzed with electroretinography (ERG) and histology. After analyzing the surface and permeability properties of PI, subretinal PI membrane transplantations with and without hESC-RPE were performed in rabbits. The rabbits were followed for three months and eyes analyzed with fundus photography, ERG, optical coherence tomography (OCT), and histology. Animals were immunosuppressed with cyclosporine the entire follow-up time. In dystrophic RCS rats, ERG and outer nuclear layer (ONL) thickness showed some rescue after hESC-RPE injection. Cells positive for human antigen were found in clusters under the retina 41 days post-injection but not anymore after 105 days. In rabbits, OCT showed good placement of the PI. However, there was loss of pigmentation on the hESC-RPE-PI over time. In the eyes with PI alone, no obvious signs of inflammation or retinal atrophy were observed. In the presence of hESC-RPE, mononuclear cell infiltration and retinal atrophy were observed around the membranes. The porous ultrathin PI membrane was well-tolerated in the subretinal space and is a promising scaffold for RPE transplantation. However, the rejection of the transplanted cells seems to be a major problem and the given immunosuppression was insufficient for reduction of xenograft induced inflammation.
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Ilmarinen
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hiidenmaa
authors.affiliation: Department of Ophthalmology, SILK, University of Tampere and Tays Eye Center, Tampere, Finland.
authors.forename: Peeter
authors.initials: P
authors.lastname: Kööbi
authors.affiliation: Department of Electronics and Communications Engineering and BioMediTech, Tampere University of Technology, Tampere, Finland.
authors.forename: Soile
authors.initials: S
authors.lastname: Nymark
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Anni
authors.initials: A
authors.lastname: Sorkio
authors.affiliation: Department of Ophthalmology, SILK, University of Tampere and Tays Eye Center, Tampere, Finland.
authors.forename: Jing-Huan
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Stanzel
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Thieltges
authors.affiliation: Santen Oy, Tampere, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Alajuuma
authors.affiliation: Santen Oy, Tampere, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Oksala
authors.affiliation: Tays Eye Center, Tampere, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kataja
authors.affiliation: Department of Ophthalmology, SILK, University of Tampere and Tays Eye Center, Tampere, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Uusitalo
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Skottman
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004596:Electroretinography; D004847:Epithelial Cells / Q000166:cytology* / Q000637:transplantation*; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D051381:Rats; D012162:Retinal Degeneration / Q000473:pathology / Q000628:therapy; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism*; D054457:Tissue Scaffolds; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome