July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Low immunogenicity and immunosuppressive property of human ES/iPS cells derived neural retina
Author Affiliations & Notes
  • Suguru Yamasaki
    Dainippon Sumitomo Pharma, Kobe, Hyogo, Japan
    Lab for Retinal Regeneration, Riken, Kobe, Hyogo, Japan
  • Sunao Sugita
    Lab for Retinal Regeneration, Riken, Kobe, Hyogo, Japan
  • Matsuri Horiuchi
    Dainippon Sumitomo Pharma, Kobe, Hyogo, Japan
    Lab for Retinal Regeneration, Riken, Kobe, Hyogo, Japan
  • atsushi kuwahara
    Dainippon Sumitomo Pharma, Kobe, Hyogo, Japan
  • Akiyoshi Kishino
    Dainippon Sumitomo Pharma, Kobe, Hyogo, Japan
  • Toru Kimura
    Dainippon Sumitomo Pharma, Kobe, Hyogo, Japan
  • Masayo Takahashi
    Lab for Retinal Regeneration, Riken, Kobe, Hyogo, Japan
  • Michiko Mandai
    Lab for Retinal Regeneration, Riken, Kobe, Hyogo, Japan
  • Footnotes
    Commercial Relationships   Suguru Yamasaki, Sumitomo Dainippon Pharma Co., Ltd (E), Sumitomo Dainippon Pharma Co., Ltd (F); Sunao Sugita, Sumitomo Dainippon Pharma Co., Ltd (F); Matsuri Horiuchi, Sumitomo Dainippon Pharma Co., Ltd (F), Sumitomo Dainippon Pharma Co., Ltd (E); atsushi kuwahara, Sumitomo Dainippon Pharma Co., Ltd (E); Akiyoshi Kishino, Sumitomo Dainippon Pharma Co., Ltd (E); Toru Kimura, Sumitomo Dainippon Pharma Co., Ltd (E); Masayo Takahashi, Sumitomo Dainippon Pharma Co., Ltd (F); Michiko Mandai, Sumitomo Dainippon Pharma Co., Ltd (F)
  • Footnotes
    Support  AMED Grant 18bm0204002h0006
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3927. doi:
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      Suguru Yamasaki, Sunao Sugita, Matsuri Horiuchi, atsushi kuwahara, Akiyoshi Kishino, Toru Kimura, Masayo Takahashi, Michiko Mandai; Low immunogenicity and immunosuppressive property of human ES/iPS cells derived neural retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3927.

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

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Abstract

Purpose : ES/iPSC-retina transplantation is a promising treatment approach for Retinitis Pigmentosa. We previously showed a long term survival, maturation, and light responsiveness of human ES/iPSC-neural retina(NR) after transplantation to end-stage retinal degeneration animal models. Although autologous transplantation is ideal, a donor-derived tissue from a patient with a disease-causing gene mutation is not adequate for therapeutic use. The purpose of this study is to examine the immunologic properties of hES/iPS-NR for future clinical application in allogeneic transplantation therapy.

Methods : The hESC (KhES-1 CRX::Venus) and the hiPSC (TLHD2) lines were differentiated into retinal tissue by SFEBq method. The expression of Human Leukocyte Antigen (HLA) class I and II at different developmental stages of hES/iPSC-NR was first tested using flow cytometry and immunohistochemistry. In immunogenicity analysis, the proliferative features of human PBMCs against hES/iPSC-NR as a tissue or enzymatically dissociated cells was evaluated by co-culture assay. The responses between autologous PBMCs and allogenic PBMCs against hiPSC-NR cell suspension was also compared. Immunosuppressive potency of hESC/iPSC-NR was also tested using PBMCs activated by agonistic CD3/CD28 antibody or mixed PBMCs of 5 donors.

Results : hESC-NR expressed neglectable level of HLA class I and II at any developmental stage from differentiation day 27 to 239. In co-culture assay, hESC/iPSC-NR cell suspension activated allogenic T lymphocytes and natural killer (NK) cells moderately while hESC/iPSC as a tissue evoked no such responses. No PBMCs proliferation was triggered by autologous iPSC-NR while a mild proliferation was observed in allogenic PBMCs using the iPSC established in our lab. Furthermore, hESC/iPSC-NR tissue strongly suppressed the proliferation of PBMCs activated by CD3/CD28 agonist antibody or mixed PBMCs. TGFβ2 was present in the hESC-NR culture medium as determined by ELISA and the immunosuppressive property was reversed by TGFβ antibody or TGFβ receptor antagonist.

Conclusions : hES/iPSC-NR showed low immunogenicity as indicated by minimal HLA class I expression and little stimulatory potency of allogenic immune cells, hES/iPSC-NR also showed some immune-suppressive property mediated by TGFβ signaling. The clinical application of hESC/iPSC-NR may compromise host immune responses in allogenic transplantation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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