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Hirofumi Uyama, Suguru Yamasaki, Yasuo Kurimoto, Masayo Takahashi, Sunao Sugita, Michiko Mandai; Survival and maturation of iPSC derived retina after transplantation in MHC matched and mismatched nonhuman primate.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3930.
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© ARVO (1962-2015); The Authors (2016-present)
Transplantation of iPSC (induced Pluripotent Stem Cells)-derived retinal tissue (iPSC-retina) is a promising approach to restore visual function in diseases with photoreceptor degeneration. The use of autologous iPSC derived tissue is ideal to avoid rejection after transplantation but it is too costly to become a standard therapy at present, and technically laborious when autologous cells contain disease causing gene mutation. The purpose of this study is to test the immunogenicity of iPSC-derived retina in allo-transplantation by evaluating survival and maturation of the graft in nonhuman primates with or without matching MHC (Major Histocompatibility Complex).
A single iPSC line derived from cynomolgus macaques with MHC homozygous haplotypes was differentiated into iPSC-retina. Focal photoreceptor degeneration was induced by laser photocoagulation and an iPSC-retina was transplanted to the degenerated area in the eye of a MHC matched and a MHC mismatched monkey. One of the alleles of MHC matched monkey was identical to the homozygote graft tissue. The graft was transplanted in the right eye and was monitored by in vivo imaging including color fundus photography, OCT (Optical Coherence Tomography) and FAG (Fluorescein Angiography) at one, 2, 4, 8, 12, and 24 weeks after surgery. The eye was collected after 6 months for histological evaluation. We also monitored the responsiveness of host immune-system against iPSC-retina by co-culturing the recipient PBMC (Peripheral Blood Mononuclear Cell) and iPSC-retina.
No evident rejection signs were observed by in vivo imaging in both MHC matched and mismatched monkeys. iPSC-retina survived and showed mature retinal cell markers including rhodopsin and cone arrestin in both MHC matched and mismatched transplantation. Histological examination showed a mild lymphocyte infiltration at the graft site only in the MHC mismatched monkey but not in the MHC matched monkey. PBMCs from MHC mismatched model showed some proliferative responses to iPSC-retina after transplantation.
iPSC-retina survived with no sign of rejection by in vivo imaging, and matured in both MHC matched and mismatched recipient monkeys without immune-suppression. A mild immune-response was suggested by histology in the MHC mismatched transplantation, which may be detected by monitoring the responsiveness of recipient’s PBMC against graft.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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