PMID- 33105725 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20210413 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 21 DP - 2020 Oct 22 TI - Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells. LID - 10.3390/ijms21217831 [doi] LID - 7831 AB - 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-beta2 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. FAU - Edo, Ayaka AU - Edo A AUID- ORCID: 0000-0001-7701-605X AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. AD - Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. FAU - Sugita, Sunao AU - Sugita S AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Futatsugi, Yoko AU - Futatsugi Y AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Sho, Junki AU - Sho J AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Onishi, Akishi AU - Onishi A AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. FAU - Kiuchi, Yoshiaki AU - Kiuchi Y AD - Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. FAU - Takahashi, Masayo AU - Takahashi M AD - Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. LA - eng GR - JP18bm0204002, JP17bk0104002/Japan Agency for Medical Research and Development/ PT - Journal Article DEP - 20201022 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (HLA Antigens) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Cell Differentiation MH - Coculture Techniques MH - Graft Rejection MH - HLA Antigens/genetics/immunology/metabolism MH - Humans MH - Immune Tolerance MH - Induced Pluripotent Stem Cells/*cytology MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed MH - Retinal Ganglion Cells/*cytology/*immunology/transplantation MH - T-Lymphocytes/*immunology MH - Transforming Growth Factor beta/metabolism PMC - PMC7660053 OTO - NOTNLM OT - immunogenicity OT - immunosuppression OT - induced pluripotent stem cells OT - mixed lymphocyte reaction OT - retinal ganglion cells COIS- The authors declare no competing interests. EDAT- 2020/10/28 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/11/01 CRDT- 2020/10/27 01:02 PHST- 2020/09/18 00:00 [received] PHST- 2020/10/08 00:00 [revised] PHST- 2020/10/20 00:00 [accepted] PHST- 2020/10/27 01:02 [entrez] PHST- 2020/10/28 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/11/01 00:00 [pmc-release] AID - ijms21217831 [pii] AID - ijms-21-07831 [pii] AID - 10.3390/ijms21217831 [doi] PST - epublish SO - Int J Mol Sci. 2020 Oct 22;21(21):7831. doi: 10.3390/ijms21217831.