July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Preclinical safety studies of hESC-derived RPE cells including tumorigenicity, biodistribution and genomic stability: a step towards treatment of Age-related Macular Degeneration
Author Affiliations & Notes
  • Sara Padrell Sánchez
    Karolinska Institutet, Stockholm, Sweden
  • Sandra Petrus-Reurer
    Karolinska Institutet, Stockholm, Sweden
  • Pankaj Kumar
    Karolinska Institutet, Stockholm, Sweden
  • Alvaro Plaza Reyes
    Karolinska Institutet, Stockholm, Sweden
  • Anders P Kvanta
    S:t Eriks Ögonsjukhus, Stockholm, Sweden
  • Fredrik Lanner
    Karolinska Institutet, Stockholm, Sweden
  • Footnotes
    Commercial Relationships   Sara Padrell Sánchez, None; Sandra Petrus-Reurer, None; Pankaj Kumar, None; Alvaro Plaza Reyes, None; Anders Kvanta, None; Fredrik Lanner, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5007. doi:
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      Sara Padrell Sánchez, Sandra Petrus-Reurer, Pankaj Kumar, Alvaro Plaza Reyes, Anders P Kvanta, Fredrik Lanner; Preclinical safety studies of hESC-derived RPE cells including tumorigenicity, biodistribution and genomic stability: a step towards treatment of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5007.

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

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Abstract

Purpose : Dry Age-related Macular Degeneration (AMD) is the leading cause of blindness in people aged 65 and older in industrialized countries. This disease is untreatable at present and its main feature is the degeneration of Retinal Pigment Epithelium (RPE), leading to a progressive photoreceptor degeneration and vision loss. We have recently established a novel xeno-free and robust hES cell in vitro differentiation protocol using human recombinant laminin 521. The hES-RPE cells have been transplanted into a large-eyed preclinical model, the rabbit, with promising functional results. Exhaustive characterizations have demonstrated that the cells obtained by this protocol share the main morphological, histological, physiological and functional features with native RPE cells, which makes these cells a good candidate for a possible AMD treatment. Since the obtained cells have been differentiated from hES cells, it cannot be ignored that a tiny fraction of undifferentiated and possibly tumorigenic cells may still reside in the final product. Therefore, before these cells could be considered for further clinical applications, exhaustive tumorigenicity tests on mice and other safety studies have to be performed in order to assess the purity and safety of the final product.

Methods : To perform the tumorigenicity studies, several groups of NOG mice have been subcutaneously injected, with increasing number of hES cells to establish how many lingering cells could generate a tumorogenic growth. In parallel, 10 million cells from three time points along the differentiation protocol have been injected. Furthermore, we have undertaken karyotyping, genotyping and whole genome sequencing of the original hES cells and the mature hES-RPE cells to evaluate the possible introduction of harmful alterations of the genome. Finally, bio-distribution of transplanted hES-RPE cells has been undertaken in transplanted rabbits and mice.

Results : All injected NOG mice have been monitored for a possible teratoma formation. 10/10 mice injected with 1 million of hES cells developed teratomas, whereas no teratoma formation has been observed in any of the mice injected with mature hES-RPE cells.

Conclusions : All these tests are showing a positive outcome, which would promote our hES-RPE cells to take a step forward into further clinical trials.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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