MHC matching improves engraftment of iPSC-derived neurons in non-human primates.
説明
type:Journal Article
The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.
収録刊行物
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- Nature Communications
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Nature Communications 8 (1), 385-, 2017-08-30
Springer Nature
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詳細情報 詳細情報について
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- CRID
- 1050001202932929024
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- NII論文ID
- 120006343783
- 120006365783
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- ISSN
- 20411723
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- HANDLE
- 2433/227001
- 10422/00012354
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- PubMed
- 28855509
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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