March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Safety study in Mini Pigs of transplanted Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (hESC-RPE)
Author Affiliations & Notes
  • Rodrigo A. Brantfernandes
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil
  • Bruno Diniz
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil
  • Ramiro Ribeiro
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
  • Yuntao Hu
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Peking University Third Hospital, Beijing, China
  • Laura Liu
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
  • Padmaja Thomas
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
  • Biju Thomas
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
  • Ashish Ahuja
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
  • David R. Hinton
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Neurosurgery and Pathology,
    University of Southern California, Keck School of Medicine, Los Angeles, California
  • Mark S. Humayun
    Ophthalmology, Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Biomedical Engineering,
    University of Southern California, Keck School of Medicine, Los Angeles, California
  • Footnotes
    Commercial Relationships  Rodrigo A. Brantfernandes, None; Bruno Diniz, None; Ramiro Ribeiro, None; Yuntao Hu, None; Laura Liu, None; Padmaja Thomas, None; Biju Thomas, None; Ashish Ahuja, None; David R. Hinton, None; Mark S. Humayun, None
  • Footnotes
    Support  CIRM
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 312. doi:
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      Rodrigo A. Brantfernandes, Bruno Diniz, Ramiro Ribeiro, Yuntao Hu, Laura Liu, Padmaja Thomas, Biju Thomas, Ashish Ahuja, David R. Hinton, Mark S. Humayun; Safety study in Mini Pigs of transplanted Human Embryonic Stem Cell Derived Retinal Pigment Epithelium (hESC-RPE). Invest. Ophthalmol. Vis. Sci. 2012;53(14):312.

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

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Abstract

Purpose: : To determine whether the surgical transplantation of a hESC- derived retinal pigment epithelium (hESC-RPE) monolayer seeded onto a parylene film into the subretinal space of pigs is a safe procedure

Methods: : All animal 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 eight 2 months old female Yucatan mini Pigs.The surgical procedure comprised a pars plana vitrectomy plus retinal detachment with balanced saline solution and a limited peripheral retinectomy for insertion of the substrate seeded with cells. Silicone oil tamponade plus laser were performed in all subjects.All subjects received oral cyclosporine (100 mg/day for the first month, 200 mg/day for the last two months) during the entire follow up.Three months after implantation, the pigs were sacrificed.Eyes and organs were fixed (Davidson’s solution and formalin, respectively), 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 (RPE-specific antigen) and TRA-1-85 (human blood group antigen).

Results: : The cell monolayer over the parylene scaffold was immunopositive for TRA-1-85 and RPE-65 three months after surgical implantation. Human cells did not migrate off the parylene substrate.In one eye there was a mild inflammatory reaction around the implant, but it was negative for human biomarkers. There was no evidence of intraocular tumor formation. Systemic organs did not show gross evidence of tumor and are now being evaluated microscopically.

Conclusions: : The hESC RPE survived for at least three months in this animal model. The surgical procedure and subretinal implantation of the substrate with cells proved feasible and safe without the induction of tumors in the eyes and organs of the immunosuppressed animals.

Keywords: retinal pigment epithelium • transplantation • age-related macular degeneration 
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