Investigative Ophthalmology & Visual Science Cover Image for Volume 57, Issue 12
September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Towards an improvement of the visual function preservation in RCS rats by transplantation of human stem-cell-derived RPE and photoreceptor precursor cells.
Author Affiliations & Notes
  • Laura Fontrodona
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Laia Miquel
    Stem Cell Bank, Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain
  • Yolanda Muñoz
    Stem Cell Bank, Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain
  • Diana Mora Ramírez
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Anna Salas Torras
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Barbara Ferreira-de-Souza
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Marina Riera
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Silvia Albert
    Stem Cell Bank, Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain
  • Anna Veiga
    Stem Cell Bank, Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain
  • Jose Garcia-Arumi
    Ophthalmology, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
  • Footnotes
    Commercial Relationships   Laura Fontrodona, None; Laia Miquel, None; Yolanda Muñoz, None; Diana Mora Ramírez, None; Anna Salas Torras, None; Barbara Ferreira-de-Souza, None; Marina Riera, None; Silvia Albert, None; Anna Veiga, None; Jose Garcia-Arumi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3731. doi:
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      Laura Fontrodona, Laia Miquel, Yolanda Muñoz, Diana Mora Ramírez, Anna Salas Torras, Barbara Ferreira-de-Souza, Marina Riera, Silvia Albert, Anna Veiga, Jose Garcia-Arumi; Towards an improvement of the visual function preservation in RCS rats by transplantation of human stem-cell-derived RPE and photoreceptor precursor cells.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3731.

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

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Abstract

Purpose : Cell therapy for retinal degenerative diseases is a newborn reality that should be constantly subjected to refinement. We used the Royal College of Surgeons (RCS) rat model to test the hypothesis that subretinal injection of a combination of photoreceptor precursor cells (PPC) and Retinal Pigmented Epithelium (RPE) cells derived from human stem cells would provide better benefits than a cell therapy uniquely using RPE cells.

Methods : We differentiated and obtained RPE and PPC from two human stem cell lines of distinct origins: embryonic stem cells (hESC) and induced pluripotent stem cells from cord blood (hiPSC). Following characterization of these cell-derived populations, five groups of p21 RCS rats received a subretinal transplant of: (i, ii) a combination of PPC and RPE from hESC or hiPSC; (iii, iv) RPE alone from hESC or hiPSC; (v) cell culture media as controls. The visual function was assessed through Ganzfeld electroretinography at several time points up to four months after injection. After determining the survival of the grafts in the host eye, we studied their capacity to integrate and function in the rat retina through histological and immunohistochemical techniques.

Results : Eyes injected with any type of cell therapy boost a significant slowdown effect on the progression of retinal degeneration compared to control eyes. Interestingly, while during the first 2 months no differences were observed between the groups that received the combined or the RPE alone treatments; upon 3 months of transplantation, eyes injected with a combination of PPC and RPE responded significantly better to light stimuli than eyes that had only received RPE cells. Such effect was observed up to 4 months after treatment and in concordance with it, at that time eyes treated with the combination of PPC and RPE displayed higher number of ONL (outer nuclear layer) cell rows than RPE alone treated eyes.

Conclusions : Our preliminary results might be pointing towards an upgraded version of the generally used RPE cell therapy if combined with PPC. We are currently characterizing the degree of integration of the grafts and to which extent these therapies are able to protect the host retinas against the degenerative process.

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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