Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

International Journal of Molecular Sciences Volume 21 Issue 21 Page 7831- published_at 2020-10-22
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Title ( eng )
Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells
Creator
Edo Ayaka
Sugita Sunao
Futatsugi Yoko
Sho Junki
Onishi Akishi
Takahashi Masayo
Source Title
International Journal of Molecular Sciences
Volume 21
Issue 21
Start Page 7831
Abstract
Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.
Keywords
retinal ganglion cells
induced pluripotent stem cells
immunogenicity
mixed lymphocyte reaction
immunosuppression
Descriptions
This work was supported by the Research Center Network for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED) to M.T., and by a Scientific Research Grant (B, 18H02959) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to S.S. A.E. was financially supported from RIKEN by a Junior Research Associate (JRA) program for graduate students.
Language
eng
Resource Type journal article
Publisher
MDPI
Date of Issued 2020-10-22
Rights
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 1661-6596
[ISSN] 1422-0067
[DOI] 10.3390/ijms21217831
[DOI] https://doi.org/10.3390/ijms21217831