MHC matching improves engraftment of iPSC-derived neurons in non-human primates

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...

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Published inNature communications Vol. 8; no. 1; pp. 385 - 12
Main Authors Morizane, Asuka, Kikuchi, Tetsuhiro, Hayashi, Takuya, Mizuma, Hiroshi, Takara, Sayuki, Doi, Hisashi, Mawatari, Aya, Glasser, Matthew F., Shiina, Takashi, Ishigaki, Hirohito, Itoh, Yasushi, Okita, Keisuke, Yamasaki, Emi, Doi, Daisuke, Onoe, Hirotaka, Ogasawara, Kazumasa, Yamanaka, Shinya, Takahashi, Jun
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.08.2017
Nature Publishing Group
Nature Portfolio
Subjects
631/250/1854/2812
631/378/1687
631/532/2064/2158
692/308/2171
Animals
Antigens
Biomarkers
Brain
Dopamine
Dopaminergic Neurons - immunology
Dopaminergic Neurons - transplantation
Female
Graft Rejection - immunology
Haplotypes
HLA Antigens - genetics
Humanities and Social Sciences
Immune response
Immune system
Immunohistochemistry
Immunology
Induced Pluripotent Stem Cells - transplantation
Life sciences
Lymphocytes
Lymphocytes - immunology
Macaca
Major histocompatibility complex
Major Histocompatibility Complex - immunology
Male
Matching
Medicine
Microglia - immunology
multidisciplinary
Neurons
Neurosciences
Parkinson's disease
Pluripotency
Positron-Emission Tomography
Primates
Science
Science (multidisciplinary)
Stem cells
Survival
Transplantation
Online AccessGet full text
ISSN2041-1723
2041-1723
DOI10.1038/s41467-017-00926-5

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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.
AbstractList 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.
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.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.
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.
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.
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.
ArticleNumber 385
Author Onoe, Hirotaka
Yamasaki, Emi
Doi, Hisashi
Okita, Keisuke
Glasser, Matthew F.
Yamanaka, Shinya
Shiina, Takashi
Mizuma, Hiroshi
Morizane, Asuka
Takara, Sayuki
Ishigaki, Hirohito
Kikuchi, Tetsuhiro
Mawatari, Aya
Itoh, Yasushi
Ogasawara, Kazumasa
Takahashi, Jun
Hayashi, Takuya
Doi, Daisuke
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  surname: Morizane
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  organization: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
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  givenname: Tetsuhiro
  orcidid: 0000-0003-2332-4967
  surname: Kikuchi
  fullname: Kikuchi, Tetsuhiro
  organization: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
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  givenname: Takuya
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  orcidid: 0000-0001-8970-9486
  surname: Mizuma
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– sequence: 5
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  organization: RIKEN Center for Life Science Technologies (CLST)
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  organization: RIKEN Center for Life Science Technologies (CLST)
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  givenname: Aya
  surname: Mawatari
  fullname: Mawatari, Aya
  organization: RIKEN Center for Life Science Technologies (CLST)
– sequence: 8
  givenname: Matthew F.
  surname: Glasser
  fullname: Glasser, Matthew F.
  organization: Department of Neuroscience, Washington University School of Medicine
– sequence: 9
  givenname: Takashi
  surname: Shiina
  fullname: Shiina, Takashi
  organization: Department of Molecular Life Science, Tokai University, School of Medicine
– sequence: 10
  givenname: Hirohito
  surname: Ishigaki
  fullname: Ishigaki, Hirohito
  organization: Department of Pathology, Shiga University of Medical Science
– sequence: 11
  givenname: Yasushi
  surname: Itoh
  fullname: Itoh, Yasushi
  organization: Department of Pathology, Shiga University of Medical Science
– sequence: 12
  givenname: Keisuke
  orcidid: 0000-0001-5806-1090
  surname: Okita
  fullname: Okita, Keisuke
  organization: Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University
– sequence: 13
  givenname: Emi
  surname: Yamasaki
  fullname: Yamasaki, Emi
  organization: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
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  givenname: Daisuke
  surname: Doi
  fullname: Doi, Daisuke
  organization: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University
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  givenname: Hirotaka
  surname: Onoe
  fullname: Onoe, Hirotaka
  organization: RIKEN Center for Life Science Technologies (CLST), Department of Neuroscience, Kyoto University Graduate School of Medicine
– sequence: 16
  givenname: Kazumasa
  surname: Ogasawara
  fullname: Ogasawara, Kazumasa
  organization: Department of Pathology, Shiga University of Medical Science
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  givenname: Shinya
  surname: Yamanaka
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  givenname: Jun
  orcidid: 0000-0003-3642-9186
  surname: Takahashi
  fullname: Takahashi, Jun
  email: jbtaka@cira.kyoto-u.ac.jp
  organization: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Department of Neurosurgery, Kyoto University Graduate School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28855509$$D View this record in MEDLINE/PubMed
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Snippet The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell...
Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched...
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StartPage 385
SubjectTerms 631/250/1854/2812
631/378/1687
631/532/2064/2158
692/308/2171
Animals
Antigens
Biomarkers
Brain
Dopamine
Dopaminergic Neurons - immunology
Dopaminergic Neurons - transplantation
Female
Graft Rejection - immunology
Haplotypes
HLA Antigens - genetics
Humanities and Social Sciences
Immune response
Immune system
Immunohistochemistry
Immunology
Induced Pluripotent Stem Cells - transplantation
Life sciences
Lymphocytes
Lymphocytes - immunology
Macaca
Major histocompatibility complex
Major Histocompatibility Complex - immunology
Male
Matching
Medicine
Microglia - immunology
multidisciplinary
Neurons
Neurosciences
Parkinson's disease
Pluripotency
Positron-Emission Tomography
Primates
Science
Science (multidisciplinary)
Stem cells
Survival
Transplantation
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Title MHC matching improves engraftment of iPSC-derived neurons in non-human primates
URI https://link.springer.com/article/10.1038/s41467-017-00926-5
https://www.ncbi.nlm.nih.gov/pubmed/28855509
https://www.proquest.com/docview/1933903086
https://www.proquest.com/docview/1934286321
https://pubmed.ncbi.nlm.nih.gov/PMC5577234
https://doaj.org/article/37518cb36fd0402692f5bdd69bd784da
Volume 8
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