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Fabian Thieltges, Tanja Ilmarinen, Hanna Hiidenmaa, Frank G Holz, Heli Skottman, Boris V Stanzel; Subretinal implantation of human embryonic stem cell derived RPE on ultrathin polyester carriers in rabbits.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1824.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the influence of subretinal xenotransplantation of human embryonic stem cell (hESC) derived retinal pigment epithelium (RPE) grown on porous ultrathin carriers in rabbits on retinal preservation.
The hESC-RPE cells were differentiated from two different hESC lines with a previously established xeno-free protocol. The differentiated RPE cells were seeded on human recombinant laminin coated polyethylene terephthalate (PET) inserts with 1.0 µm pores for maturation and characterized by their morphology and polarity, expression of differentiation markers, and phagocytosis activity. Live hESC-RPE monolayer cultured on PET were shipped from Finland to Germany in optimized transportation conditions. TER was measured pre- and post transport. Following vitrectomy, bleb retinal detachments (bRD) were raised with balanced salt solution (BSS) in the eyes of 10 pigmented rabbits. Using custom-made surgical instrumentation, hESC-RPE monolayers on PET were xenotransplanted into the subretinal space (SRS) created by the bRD (N=9). Some of these animals (N=2) received weekly intravitreal injections of the immunosuppressant FK506. As a control, PET without cells was implanted into SRS (N=1). Rabbits were weekly monitored by SD-OCT after implantation. After 4 weeks, the eyes were processed for histology.
Human ESC-RPE cells displayed typical RPE characteristics. A logistic protocol for shipment of live hESC-RPE could be established, with comparable pre- and post transport TER and morphology. SD-OCT showed steady positioned implants with an adherent retina over the implant after 4 weeks. A nearly intact xenografted hESC-RPE monolayer could be observed at 4 weeks post implantation to rabbit SRS. SD-OCT and histology showed nearly preserved retinal layers overlying hESC-RPE in some animals (N=5), while in others retinal atrophy appeared at 1 week (N=4). Pilot experiments with intravitreal application of FK506 appeared to alleviate retinal thinning. Control implant with PET alone showed reduced outer retinal thickness without signs of inflammation.
These preliminary data suggest for the first time subretinal tolerance of a hESC-RPE monolayer xenotransplant along with improved retinal preservation in rabbits.
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