Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Stem Cell Reports. 2022 Nov 8;17(11):2392-2408. doi: 10.1016/j.stemcr.2022.09.014. Epub 2022 Oct 27.
Transplantation of embryonic/induced pluripotent stem cell-derived retina (ESC/iPSC-retina) restores host retinal ganglion cell light responses in end-stage retinal degeneration models with host-graft synapse formation. We studied the immunological features of iPSC-retina transplantation using major histocompatibility complex (MHC)-homozygote monkey iPSC-retinas in monkeys with laser-induced retinal degeneration in MHC-matched and -mismatched transplantation. MHC-mismatched transplantation without immune suppression showed no evident clinical signs of rejection and histologically showed graft maturation without lymphocytic infiltration, although immunological tests using peripheral blood monocytes suggested subclinical rejection in three of four MHC-mismatched monkeys. Although extensive photoreceptor rosette formation was observed on histology, evaluation of functional integration using mouse models such as mouse ESC-retina (C57BL/6) transplanted into rd1(C3H/HeJ, MHC-mismatched model) elicited light responses in the host retinal ganglion cells after transplantation but with less responsiveness than that in rd1-2J mice (C57BL/6, MHC-matched model). These results suggest the reasonable use of ESC/iPSC-retina in MHC-mismatched transplantation, albeit with caution.
胚胎/诱导多能干细胞源性视网膜（ESC/iPSC-视网膜）移植可在晚期视网膜变性模型中恢复宿主视网膜神经节细胞的光反应，形成宿主-移植物突触。我们使用 MHC 纯合猴 ESC-视网膜在 MHC 匹配和不匹配移植的激光诱导视网膜变性的猴中研究了 iPSC-视网膜移植的免疫学特征。MHC 不匹配移植而不进行免疫抑制显示出没有明显的排斥临床迹象，组织学上显示移植物成熟而没有淋巴细胞浸润，尽管使用外周血单核细胞进行的免疫学测试表明在四只 MHC 不匹配的猴子中有三只存在亚临床排斥。尽管在组织学上观察到广泛的光感受器玫瑰花结形成，但使用小鼠 ESC-视网膜（C57BL/6）移植到 rd1（C3H/HeJ，MHC 不匹配模型）等小鼠模型评估功能整合，在移植后可在宿主视网膜神经节细胞中引发光反应，但反应性低于 rd1-2J 小鼠（C57BL/6，MHC 匹配模型）。这些结果表明，尽管需要谨慎，但在 MHC 不匹配移植中合理使用 ESC/iPSC-视网膜是合理的。
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