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Title: Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer
Authors: Diniz, Bruno [UNIFESP]
Thomas, Padmaja
Thomas, Biju
Ribeiro, Ramiro [UNIFESP]
Hu, Yuntao
Brant, Rodrigo [UNIFESP]
Ahuja, Ashish
Zhu, Danhong
Liu, Laura
Koss, Michael
Maia, Mauricio [UNIFESP]
Chader, Gerald
Hinton, David R.
Humayun, Mark S.
Doheny Eye Inst
Universidade Federal de São Paulo (UNIFESP)
Univ So Calif
Hosp Univ Curitiba
Peking Univ
Chang Gung Mem Hosp
Goethe Univ Frankfurt
Keywords: age-related macular degeneration
retinal pigment epithelium
human embryonic stem cells
Issue Date: 1-Jul-2013
Publisher: Assoc Research Vision Ophthalmology Inc
Citation: Investigative Ophthalmology & Visual Science. Rockville: Assoc Research Vision Ophthalmology Inc, v. 54, n. 7, p. 5087-5096, 2013.
Abstract: PURPOSE. To evaluate cell survival and tumorigenicity of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM).METHODS. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker).RESULTS. the implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group.CONCLUSIONS. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. the lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects.
ISSN: 0146-0404
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