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Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets
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 plur...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287743/ https://www.ncbi.nlm.nih.gov/pubmed/35750044 http://dx.doi.org/10.1016/j.stemcr.2022.05.018 |
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author | Yoshinaga, Yu Soma, Takeshi Azuma, Shohei Maruyama, Kazuichi Hashikawa, Yoshiko Katayama, Tomohiko Sasamoto, Yuzuru Takayanagi, Hiroshi Hosen, Naoki Shiina, Takashi Ogasawara, Kazumasa Hayashi, Ryuhei Nishida, Kohji |
author_facet | Yoshinaga, Yu Soma, Takeshi Azuma, Shohei Maruyama, Kazuichi Hashikawa, Yoshiko Katayama, Tomohiko Sasamoto, Yuzuru Takayanagi, Hiroshi Hosen, Naoki Shiina, Takashi Ogasawara, Kazumasa Hayashi, Ryuhei Nishida, Kohji |
author_sort | Yoshinaga, Yu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9287743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92877432022-07-17 Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets Yoshinaga, Yu Soma, Takeshi Azuma, Shohei Maruyama, Kazuichi Hashikawa, Yoshiko Katayama, Tomohiko Sasamoto, Yuzuru Takayanagi, Hiroshi Hosen, Naoki Shiina, Takashi Ogasawara, Kazumasa Hayashi, Ryuhei Nishida, Kohji Stem Cell Reports Article 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. Elsevier 2022-06-23 /pmc/articles/PMC9287743/ /pubmed/35750044 http://dx.doi.org/10.1016/j.stemcr.2022.05.018 Text en © 2022. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Yoshinaga, Yu Soma, Takeshi Azuma, Shohei Maruyama, Kazuichi Hashikawa, Yoshiko Katayama, Tomohiko Sasamoto, Yuzuru Takayanagi, Hiroshi Hosen, Naoki Shiina, Takashi Ogasawara, Kazumasa Hayashi, Ryuhei Nishida, Kohji Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title | Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title_full | Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title_fullStr | Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title_full_unstemmed | Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title_short | Long-term survival in non-human primates of stem cell-derived, MHC-unmatched corneal epithelial cell sheets |
title_sort | long-term survival in non-human primates of stem cell-derived, mhc-unmatched corneal epithelial cell sheets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287743/ https://www.ncbi.nlm.nih.gov/pubmed/35750044 http://dx.doi.org/10.1016/j.stemcr.2022.05.018 |
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