Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only