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Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes
The loss of functional cells through immunological rejection after transplantation reduces the efficacy of regenerative therapies for cardiac failure that use allogeneic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Recently, mixed-chimera mice with donor-specific immunotolerance...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890721/ https://www.ncbi.nlm.nih.gov/pubmed/35235568 http://dx.doi.org/10.1371/journal.pone.0264317 |
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author | Yoshida, Shohei Miyagawa, Shigeru Matsuzaki, Takashi Ishii, Yasuyuki Fukuda-Kawaguchi, Emi Kawamura, Takuji Kawamura, Ai Nakamura, Yuki Toda, Koichi Sawa, Yoshiki |
author_facet | Yoshida, Shohei Miyagawa, Shigeru Matsuzaki, Takashi Ishii, Yasuyuki Fukuda-Kawaguchi, Emi Kawamura, Takuji Kawamura, Ai Nakamura, Yuki Toda, Koichi Sawa, Yoshiki |
author_sort | Yoshida, Shohei |
collection | PubMed |
description | The loss of functional cells through immunological rejection after transplantation reduces the efficacy of regenerative therapies for cardiac failure that use allogeneic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Recently, mixed-chimera mice with donor-specific immunotolerance have been established using the RGI-2001 (liposomal formulation of α-galactosyl ceramide) ligand, which activates invariant natural killer T (iNKT) cells. The present study aimed to investigate whether mixed chimerism, established using RGI-2001, prolongs graft survival in allogeneic iPSC-CM transplantation. Mixed-chimera mice were established via combinatorial treatment with RGI-2001 and anti-CD154 antibodies in an irradiated murine bone marrow transplant model. Luciferase-expressing allogeneic iPSC-CMs were transplanted into mixed-chimera and untreated mice, followed by in vivo imaging. RGI-2001 enhanced iNKT cell activation in mice, and mixed chimerism was successfully established. In vivo imaging revealed that while the allografts were completely obliterated within 2 weeks when transplanted to untreated mice, their survivals were not affected in the mixed-chimera mice. Furthermore, numerous CD3+ cells infiltrated allografts in untreated mice, but fewer CD3+ cells were present in mixed-chimera mice. We conclude that mixed-chimera mice established using RGI-2001 showed prolonged graft survival after allogeneic iPSC-CM transplantation. This donor-specific immunotolerance might increase the efficacy of regenerative therapies for heart failure with allogeneic iPSC-CMs. |
format | Online Article Text |
id | pubmed-8890721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88907212022-03-03 Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes Yoshida, Shohei Miyagawa, Shigeru Matsuzaki, Takashi Ishii, Yasuyuki Fukuda-Kawaguchi, Emi Kawamura, Takuji Kawamura, Ai Nakamura, Yuki Toda, Koichi Sawa, Yoshiki PLoS One Research Article The loss of functional cells through immunological rejection after transplantation reduces the efficacy of regenerative therapies for cardiac failure that use allogeneic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Recently, mixed-chimera mice with donor-specific immunotolerance have been established using the RGI-2001 (liposomal formulation of α-galactosyl ceramide) ligand, which activates invariant natural killer T (iNKT) cells. The present study aimed to investigate whether mixed chimerism, established using RGI-2001, prolongs graft survival in allogeneic iPSC-CM transplantation. Mixed-chimera mice were established via combinatorial treatment with RGI-2001 and anti-CD154 antibodies in an irradiated murine bone marrow transplant model. Luciferase-expressing allogeneic iPSC-CMs were transplanted into mixed-chimera and untreated mice, followed by in vivo imaging. RGI-2001 enhanced iNKT cell activation in mice, and mixed chimerism was successfully established. In vivo imaging revealed that while the allografts were completely obliterated within 2 weeks when transplanted to untreated mice, their survivals were not affected in the mixed-chimera mice. Furthermore, numerous CD3+ cells infiltrated allografts in untreated mice, but fewer CD3+ cells were present in mixed-chimera mice. We conclude that mixed-chimera mice established using RGI-2001 showed prolonged graft survival after allogeneic iPSC-CM transplantation. This donor-specific immunotolerance might increase the efficacy of regenerative therapies for heart failure with allogeneic iPSC-CMs. Public Library of Science 2022-03-02 /pmc/articles/PMC8890721/ /pubmed/35235568 http://dx.doi.org/10.1371/journal.pone.0264317 Text en © 2022 Yoshida et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yoshida, Shohei Miyagawa, Shigeru Matsuzaki, Takashi Ishii, Yasuyuki Fukuda-Kawaguchi, Emi Kawamura, Takuji Kawamura, Ai Nakamura, Yuki Toda, Koichi Sawa, Yoshiki Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title | Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title_full | Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title_fullStr | Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title_full_unstemmed | Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title_short | Chimerism through the activation of invariant natural killer T cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
title_sort | chimerism through the activation of invariant natural killer t cells prolongs graft survival after transplantation of induced pluripotent stem cell–derived allogeneic cardiomyocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890721/ https://www.ncbi.nlm.nih.gov/pubmed/35235568 http://dx.doi.org/10.1371/journal.pone.0264317 |
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