March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Embryonic Stem Cell Derived Retinal Pigment Epithelium Stem Cell Transplant: Survival And Lack Of Tumor Formation In Athymic Nude Rats
Author Affiliations & Notes
  • Bruno Diniz, Sr.
    Doheny Eye Institute, University of Southern California, Los Angeles, California
    Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil
  • Ramiro Ribeiro
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • Rodrigo Brant
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • Yuntao Hu
    Doheny Eye Institute, University of Southern California, Los Angeles, California
    Department of Ophthalmology, Peking University Third Hospital, Beijing, China
  • Laura Liu
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • Padmaja Thomas
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • Biju Thomas
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • David Hinton
    Doheny Eye Institute, University of Southern California, Los Angeles, California
    Keck School of Medicine, Los Angeles, California
  • Mark Humayun
    Doheny Eye Institute, University of Southern California, Los Angeles, California
  • Footnotes
    Commercial Relationships  Bruno Diniz, Sr., None; Ramiro Ribeiro, None; Rodrigo Brant, None; Yuntao Hu, None; Laura Liu, None; Padmaja Thomas, None; Biju Thomas, None; David Hinton, None; Mark Humayun, None
  • Footnotes
    Support  NEI EY03040, California Institute for Regenerative Medicine (CIRM)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5922. doi:https://doi.org/
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      Bruno Diniz, Sr., Ramiro Ribeiro, Rodrigo Brant, Yuntao Hu, Laura Liu, Padmaja Thomas, Biju Thomas, David Hinton, Mark Humayun; Embryonic Stem Cell Derived Retinal Pigment Epithelium Stem Cell Transplant: Survival And Lack Of Tumor Formation In Athymic Nude Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5922. doi: https://doi.org/.

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

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Abstract

Purpose: : Assessments of safety and efficacy are crucial before human embryonic stem cell (hESC) therapies can move into the clinic. Our purpose is to determine whether transplantation of a hESC- derived retinal pigment epithelium (hESC-RPE) monolayer into the subretinal space of nude rats has a tumorigenic effect.

Methods: : All procedures were performed according IACUC and ARVO rules regarding animal studies. Ultrathin films made from parylene were seeded with hESC-RPE and surgically implanted in the subretinal space of twelve athymic nude rats (male, n= 6 female, n=6). Six months after implantation, the rats were sacrificed. Eyes and organs (brain, liver, kidneys, spleen, heart and lungs) were fixed in formaldehyde, embedded in paraffin, and subjected to histological analysis based on hematoxylin and eosin (HE) staining. Adjacent sections were processed for immunohistochemical analysis (when needed) using the following antibodies: anti-RPE65 and TRA-1-85.

Results: : The cell monolayer over the parylene scaffold was immunopositive for TRA-1-85 and RPE-65 marker. In two eyes we found a mild inflammatory reaction around the implant that was negative for human biomarkers. Gross morphologic and histological analysis of the systemic organs at 6 months after the surgery exhibited no evidence of neoplastic formation.

Conclusions: : The hESC-RPE can survive for at least six months in this animal model. The absence of tumor in an immunodeficient animal model (Athymic nude rat) bodes well and supports the fact that the risk of tumor formation will be highly unlikely in an immunocompetent recipient.

Keywords: retinal pigment epithelium • age-related macular degeneration 
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