September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Human embryonic stem cell-derived retinal pigment epithelial cells functionally integrate and rescue photoreceptors in a large-eyed model of geographic atrophy
Author Affiliations & Notes
  • Sandra Petrus-Reurer
    Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska Institutet, St. Erik Eye Hospital, Stockholm, Sweden
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Alvaro Plaza Reyes
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Liselotte Antonsson
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Sonya Stenfelt
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Hammurabi Bartuma
    Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska Institutet, St. Erik Eye Hospital, Stockholm, Sweden
  • Sarita Panula
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Helder Andre
    Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska Institutet, St. Erik Eye Hospital, Stockholm, Sweden
  • Outi Hovatta
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Fredrik Lanner
    Department of Clinical Sciences, Intervention and Technology, Karolinska Insitutet, Stockholm, Sweden
  • Anders P Kvanta
    Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska Institutet, St. Erik Eye Hospital, Stockholm, Sweden
  • Footnotes
    Commercial Relationships   Sandra Petrus-Reurer, None; Alvaro Plaza Reyes, None; Liselotte Antonsson, None; Sonya Stenfelt, None; Hammurabi Bartuma, None; Sarita Panula, None; Helder Andre, None; Outi Hovatta, None; Fredrik Lanner, None; Anders Kvanta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Sandra Petrus-Reurer, Alvaro Plaza Reyes, Liselotte Antonsson, Sonya Stenfelt, Hammurabi Bartuma, Sarita Panula, Helder Andre, Outi Hovatta, Fredrik Lanner, Anders P Kvanta; Human embryonic stem cell-derived retinal pigment epithelial cells functionally integrate and rescue photoreceptors in a large-eyed model of geographic atrophy. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : Human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells could replace lost tissue in geographic atrophy (GA) but efficacy has yet to be demonstrated in a large-eyed model. Here we describe a xeno-free and defined differentiation method for hESC-RPE and explore their integration and function in a large-eyed model of GA.

Methods : Xeno-free and defined derivation of hESC-RPE cultures was explored using different Bruch's membrane-associated laminin matrices. Derived cells were analyzed for purity, surface marker-expression, polarity and function using flow cytometry, immunohistochemistry, and assays for directed growth factor secretion, transepithelial resistance, and phagocytosis respectively. Suspensions of differentiated cells were transplanted subretinally into a novel rabbit model of GA and cell fate and in vivo function was analyzed by immunohistochemistry and real-time high-resolution imaging.

Results : Highly homogeneous populations of mature, polarized and functional hESC-RPE were obtained on all laminins tested with the highest yield observed using human recombinant laminin-521. Subretinal transplants of laminin-521-derived hESC-RPE in suspension integrated as polarized monolayers that exhibited phagocytic and photoreceptor rescue capacity for up to 8 months.

Conclusions : Altogether, we have developed a xeno-free and defined hESC-RPE differentiation method and present the first evidence of functional integration of clinically compliant hESC-RPE in a large-eyed GA model.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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