June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Ultrathin polyimide membrane as potential carrier for subretinal transplantation of human embryonic stem cell derived RPE
Author Affiliations & Notes
  • Tanja Ilmarinen
    BioMediTech, University of Tampere, Tampere, Finland
  • Hanna Hiidenmaa
    BioMediTech, University of Tampere, Tampere, Finland
  • Peeter Kööbi
    Department of Ophthalmology, SILK, University of Tampere and Tays Eye Center, Tampere, Finland
  • Soile Nymark
    Tampere University of Technology, Department of Electronics and Communications Engineering, BioMediTech, Tampere, Finland
  • Anni Sorkio
    BioMediTech, University of Tampere, Tampere, Finland
  • Jing-Huan Wang
    Department of Ophthalmology, SILK, University of Tampere, Tampere, Finland
  • Paivi T Alajuuma
    Santen Oy, Tampere, Finland
  • Olli E Oksala
    Santen Oy, Tampere, Finland
  • Hannu M T Uusitalo
    Department of Ophthalmology, SILK, University of Tampere and Tays Eye Center, Tampere, Finland
  • Heli Skottman
    BioMediTech, University of Tampere, Tampere, Finland
  • Footnotes
    Commercial Relationships Tanja Ilmarinen, Santen Oy (F); Hanna Hiidenmaa, None; Peeter Kööbi, None; Soile Nymark, None; Anni Sorkio, None; Jing-Huan Wang, None; Paivi Alajuuma, Santen Oy (E); Olli Oksala, Santen Oy (E); Hannu Uusitalo, None; Heli Skottman, Santen Oy (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1825. doi:
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      Tanja Ilmarinen, Hanna Hiidenmaa, Peeter Kööbi, Soile Nymark, Anni Sorkio, Jing-Huan Wang, Paivi T Alajuuma, Olli E Oksala, Hannu M T Uusitalo, Heli Skottman; Ultrathin polyimide membrane as potential carrier for subretinal transplantation of human embryonic stem cell derived RPE. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1825.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Transplantation of retinal pigment epithelium (RPE) differentiated from human pluripotent stem cells is a potential treatment strategy for age-related macular degeneration (AMD). In recent phase 1/2 trials for RPE-related disease, hPSC-RPE cells are implanted either as cell suspensions or sheets without an artificial scaffold. In many studies, including our own, suspended RPE fail to survive or function in the long-term. A scaffold would facilitate surgical handling of the graft and potentially mimic healthy Bruch’s membrane. Previously, we have shown that polyimide (PI) membrane is suitable for hESC-RPE growth. In this study, we investigated PI as a carrier for subretinal implantation of hESC-RPE in rabbits.

Methods: The surface properties of ultrathin (7.6 µm) PI membranes were investigated with scanning electron microscopy (SEM) and atomic force microscopy (AFM). Laminin coated PI membranes seeded with hESC-RPE were implanted in the subretinal space of five New Zealand White rabbits, three rabbits received PI alone, and one rabbit served as surgical control. Animals received oral cyclosporine (90 mg/day) the entire follow-up time. In vivo follow-up was performed with fundus photography and electroretinography (ERG). Optical coherence topography (OCT) was performed as an endpoint analysis. Three months after implantation, the rabbits were sacrificed and eyes subjected to histological analysis.

Results: In SEM and AFM, PI showed excellent porosity compared to polyethylene terephthalate membranes regularly used for hESC-RPE culture. After transplantation, a gradual loss of pigmentation on hESC-RPE-PI implants was observed, potentially due to cell death of the hESC-RPE cells. ERG did not show any considerable changes between the operated and fellow eyes. OCT showed good placement and biocompatibility of the implant. There was no evidence of intraocular tumors. In the eyes with PI alone, no obvious signs of inflammation or retinal atrophy were observed. However, mononuclear cell infiltration and retinal atrophy were observed around the implants in the presence of hESC-RPE on the PI.

Conclusions: The ultrathin PI membrane was well-tolerated in the subretinal space in our rabbit model and thus suitable for RPE transplantation. The oral immunosuppression was potentially insufficient for reduction of xenograft induced inflammation and needs to be adjusted in the future.

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