4.6 Article

Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets

期刊

STEM CELL REPORTS
卷 17, 期 7, 页码 1714-1729

出版社

CELL PRESS
DOI: 10.1016/j.stemcr.2022.05.018

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资金

  1. Japan Agency for Medical Research and Development (AMED) [JP19bk0104080h, JP19bm0504005h]
  2. Osaka Eye Bank Research Grant 2020

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This study investigated the impact of human leukocyte antigen (HLA) on corneal epithelial cell sheet (CEPS) transplantation. The results showed that there was no difference in immune response to CEPS between HLA-matched and -unmatched peripheral blood mononuclear cells. Additionally, programmed death ligand 1 was identified to have an immunosuppressive effect on CEPS under inflammatory conditions.
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.

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