Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan.
Department of Innovative Visual Science, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan.
Stem Cell Reports. 2022 Jul 12;17(7):1714-1729. doi: 10.1016/j.stemcr.2022.05.018. Epub 2022 Jun 23.
When corneal epithelial stem cells residing in the corneal limbus become dysfunctional, called a limbal stem cell deficiency (LSCD), corneal transparency is decreased, causing severe vision loss. Transplantation of corneal epithelial cell sheets (CEPS) derived from stem cells, including induced pluripotent stem cells, is a promising treatment for LSCD. However, the potential effect of human leukocyte antigen (HLA) concordance on CEPS transplantation has not been addressed. Here, we show that there is no difference in the immune response to CEPS between HLA-matched and -unmatched peripheral blood mononuclear cells in mixed lymphocyte reactions. CEPS transplantation in cynomolgus monkeys revealed that the immune response to major histocompatibility-unmatched CEPS was not strong and could be controlled by local steroid administration. Furthermore, programmed death ligand 1 was identified as an immunosuppressive molecule in CEPS under inflammatory conditions in vitro. Our results indicate that corneal epithelium has low immunogenicity and allogeneic CEPS transplantation requires mild immunosuppression.
当位于角膜缘的角膜上皮干细胞功能失调时，称为角膜缘干细胞缺乏症（LSCD），角膜透明度降低，导致严重的视力丧失。来源于干细胞的角膜上皮细胞片（CEPS）的移植，包括诱导多能干细胞，是 LSCD 的一种有前途的治疗方法。然而，人类白细胞抗原（HLA）一致性对 CEPS 移植的潜在影响尚未得到解决。在这里，我们表明在混合淋巴细胞反应中，HLA 匹配和不匹配的外周血单核细胞对 CEPS 的免疫反应没有差异。在食蟹猴中进行的 CEPS 移植表明，对主要组织相容性不匹配的 CEPS 的免疫反应并不强烈，可以通过局部类固醇给药来控制。此外，程序性死亡配体 1 被鉴定为体外炎症条件下 CEPS 中的一种免疫抑制分子。我们的结果表明，角膜上皮具有低免疫原性，同种异体 CEPS 移植需要轻度免疫抑制。
