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Establishment of an experimental model for MHC homo-to-hetero transplantation
Open accessAbstract
Preventing rejection is a major challenge in transplantation medicine, even when using pluripotent stem cell-derived grafts. In iPS cell (iPSC)-based transplantation, to reduce the risk of rejection, it is thought to be optimal that preparing the cells from donors whose human leukocyte antigen-haplotype are homozygous. Generally, this approach is referred to as major histocompatibility complex (MHC) homo-to-hetero transplantation, which is MHC-matched but minor antigen-mismatched. To investigate the immune response in the MHC homo-to-hetero transplantation, we established a murine experimental system in which MHC-matched but minor antigen-mismatched tissue (skin) grafts were transplanted into MHC-heterozygous recipients. Unexpectedly, only minor antigen-mismatched grafts were rejected at the same time points as rejection of fully allogeneic grafts. A vigorous anti-donor type T cell response was detected in vitro and conventional immunosuppressants targeting T cell activation had limited effects on controlling rejection. However, anti-donor antibodies were not detected only in the minor antigen-mismatched transplantation. This murine transplantation model can be used to further analyze immunological subjects for MHC homo-to-hetero iPSC-based transplantation.
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“There are various antigens other than MHC molecules, so-called minor histocompatibility antigens, which interact with MHC molecules to activate T cells.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [5]
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“Minor antigen-mismatched grafts could be potent enough to cause rejection in MHC-matched grafts [5].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [5]
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Taylor, C. J., Peacock, S., Chaudhry, A. N., Bradley, J. A., & Bolton, E. M. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.07.014 · Cited by 428
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Research works printed but not linked: 17
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Cited by
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Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316
“Minor antigen-mismatched grafts could be potent enough to cause rejection in MHC-matched grafts [5].”
Background
Metadata
- Authors
- Murata, T., Wada, H., Otsuka, R., Sasaki, A., Tsuji, H., Itoh, M., Eguchi, N., Kawai, T., & Seino, K.-I.
- Affiliations
- Hokkaido University (JP)
- Massachusetts General Hospital (US)
- Corresponding author
- Seino, Ken-ichiro
- Venue
- Scientific Reports
- Published
- 2020-08-11
- Volume
- 10
- Issue
- 1
- Pages
- 13560-13560
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7421494
- OpenAlex
- W3048669947
- Cited by
- 10
- References
- 1
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 2
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion, cc-by)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Agency for Medical Research and Development
- TERUMO LIFE SCIENCE FOUNDATION
- Topics
- Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- graft rejection, skin grafts, immunosuppressants, anti-donor antibodies, murine transplantation model, HLA haplotype matching
- MeSH terms
- Animals, Female, Graft Rejection, Graft Survival, Histocompatibility Antigens, Isoantibodies, Male, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Inbred C57BL, Models, Theoretical, Tissue Donors, Transplantation, Heterologous, Transplantation, Homologous, Skin Transplantation, Mice
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