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MHC matching improves engraftment of iPSC-derived neurons in non-human primates.
- Source :
-
Nature communications [Nat Commun] 2017 Aug 30; Vol. 8 (1), pp. 385. Date of Electronic Publication: 2017 Aug 30. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Animals
Dopaminergic Neurons immunology
Female
Haplotypes
Immunohistochemistry
Lymphocytes immunology
Macaca
Male
Microglia immunology
Positron-Emission Tomography
Dopaminergic Neurons transplantation
Graft Rejection immunology
HLA Antigens genetics
Induced Pluripotent Stem Cells transplantation
Major Histocompatibility Complex immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28855509
- Full Text :
- https://doi.org/10.1038/s41467-017-00926-5