Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 56, Issue 2, Pages 1051-1062Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.14-15619
Keywords
cytokine; PS cells; TGF beta
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [25293357]
- Project for Realization of Regenerative Medicine from the MEXT
- Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical's Founder
- Grants-in-Aid for Scientific Research [25293357] Funding Source: KAKEN
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PURPOSE. The purpose of this study was to determine whether human retinal pigment epithelial (RPE) cells from induced pluripotent stem (iPS) cells could inhibit T-cell activation in vitro. METHODS. Cultured iPS-derived RPE (iPS-RPE) cells were established from fresh skin tissues or dental pulp cells obtained from healthy donors or a retinal patient after informed consent was obtained. To confirm expression of the specific markers on iPS and iPS-RPE cells, immunohistochemistry, quantitative RT-PCR (qRT-PCR), and flow cytometry were performed. Target T cells were obtained from peripheral blood mononuclear cells of healthy donors. Target T cells were assessed for proliferation by incorporation of bromodeoxyuridine or carboxyfluorescein succinimidyl ester for production of cytokines such as IFN-alpha. Expression of TGFb beta and other candidate molecules by iPS-RPE cells was evaluated with flow cytometry, ELISA, multiplex cytokine array, immunohistochemistry, and qRT-PCR. RESULTS. The RPE cells we established from iPS cells had many characteristics of mature RPE cells but no characteristics of pluripotent stem cells. Cultured iPS-RPE cells inhibited cell proliferation and production of IFN-alpha by activated CD4(+) T cells. In some bystander T cells, iPS-derived RPE cells induced CD25(+)Foxp3(+) regulatory T cells in vitro. Induced pluripotent stem-RPE cells constitutively expressed TGF beta and suppressed activation of T cells via soluble TGF beta, because TGF beta-downregulated iPS-RPE cells did not inhibit this T-cell activation. CONCLUSIONS. Cultured iPS-derived retinal cells fully suppress T-cell activation. Transplantation of iPS-RPE cells into the eye might be a therapy for retinal disorders.
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