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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)
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.
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.
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.
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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