July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Co-grafted sheets of hESC derived retina organoids and RPE improve vision function in RCS rats
Author Affiliations & Notes
  • Bin Lin
    Stem Cell Research Center, University of California at Irvine, Irvine, California, United States
  • Juan Carlos Martinez
    Department of Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States
    USC Dr. Allen and Ginsburg Institute for Biomedical Therapeutics, Los Angeles, California, United States
  • Dan Hong Zhu
    Department of Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States
    Department of Pathology, Keck School of Medicine, USC, Los Angeles, California, United States
  • David R Hinton
    Department of Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States
    Department of Pathology, Keck School of Medicine, USC, Los Angeles, California, United States
  • Mark Humayun
    Department of Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States
    USC Dr. Allen and Ginsburg Institute for Biomedical Therapeutics, Los Angeles, California, United States
  • Bryce McLelland
    Stem Cell Research Center, University of California at Irvine, Irvine, California, United States
  • Robert Aramant
    Stem Cell Research Center, University of California at Irvine, Irvine, California, United States
  • Magdalene J Seiler
    Stem Cell Research Center, University of California at Irvine, Irvine, California, United States
    Ophthalmology, UC Irvine, School of Medicine, Irvine, California, United States
  • Biju Thomas
    Department of Ophthalmology, USC Roski Eye Institute, Los Angeles, California, United States
    USC Dr. Allen and Ginsburg Institute for Biomedical Therapeutics, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Bin Lin, None; Juan Carlos Martinez, None; Dan Hong Zhu, None; David Hinton, Regenerative Patch Technologies LLC (I), Regenerative Patch Technologies LLC (P), Regenerative Patch Technologies LLC (C), Regenerative Patch Technologies LLC (S); Mark Humayun, Regenerative Patch Technologies LLC (I), Regenerative Patch Technologies LLC (P), Regenerative Patch Technologies LLC (C), Regenerative Patch Technologies LLC (S); Bryce McLelland, None; Robert Aramant, Ocular Transplantation LLC (P), Ocular Transplantation LLC (E); Magdalene Seiler, Ocular Transplantation LLC (P); Biju Thomas, None
  • Footnotes
    Support  CIRM DISC1-09912 (BBT), CIRM DT1 (MSH), CIRM TR4-06648 (MJS), NIH R01EY024045 (HSK), UCI Bridge funds (MJS); CIRM TR1-10995 (MJS); Bright Focus Foundation (BBT)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2890. doi:
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    • Get Citation

      Bin Lin, Juan Carlos Martinez, Dan Hong Zhu, David R Hinton, Mark Humayun, Bryce McLelland, Robert Aramant, Magdalene J Seiler, Biju Thomas; Co-grafted sheets of hESC derived retina organoids and RPE improve vision function in RCS rats. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2890.

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

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Abstract

Purpose : To develop a cellular therapy for retinal diseases caused by degeneration of both photoreceptors and retinal pigment epithelium (RPE). In previous studies, co-grafted sheets of fetal retina with its RPE have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue.

Methods : Co-grafts made of human embryonic stem cells (hESC) derived RPE sheets on parylene together with sheets of retina organoids (RO) was transplanted into a rat model of RPE and photoreceptor dysfunction (immunodeficient Royal College of Surgeon (RCS) rats), The H9 derived CRX-GFP expressing hESC cell line (Collin et al. 2016, Stem Cells 34:311–321) was differentiated into retina organoids (Zhong et al. 2014). H9 hESC were also cultured and spontaneously differentiated to RPE cells. For the preparation of hESC-RPE+RO co-grafts, RO sheets were dissected out and combined with RPE implants using the bio-adhesive agent alginate. The co-grafts were surgically placed into the subretinal space of RCS rats (2 months old male and females, n=20). Growth and development of transplants was evaluated by Optical Coherence Tomography (OCT). Visual function was tested by optokinetic testing (OKT), electroretinogram (ERG) and electrophysiological recording in the superior colliculus (SC recording). Histological assessments were performed using H&E staining and immunohistochemistry.

Results : Retina co-grafts can be prepared by combining RPE (supported by an artificial Bruch’s membrane) and RO sheets, using alginate as adhesive which provided gentle encapsulation. OCT imaging demonstrated successful surgical implantation of the co-grafts. Histological evaluation confirmed the survival and development of the co-grafts. OKT, ERG and SC recording showed significant vision improvement.

Conclusions : The study supports the possibility of combining RPE+RO into a co-graft, which can be surgically placed into the subretinal space, mature and improve vision function. This novel tissue engineering technique can become a new cellular therapy for complete replacement of a degenerated retina.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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