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Immunogenicity of human embryonic stem cell-derived beta cells

Aims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine... Full description

Journal Title: Diabetologia 2016-10-27, Vol.60 (1), p.126-133
Main Author: van der Torren, Cornelis R
Other Authors: Zaldumbide, Arnaud , Duinkerken, Gaby , Brand-Schaaf, Simone H , Peakman, Mark , Stangé, Geert , Martinson, Laura , Kroon, Evert , Brandon, Eugene P , Pipeleers, Daniel , Roep, Bart O
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/27787618
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6518073
title: Immunogenicity of human embryonic stem cell-derived beta cells
format: Article
creator:
  • van der Torren, Cornelis R
  • Zaldumbide, Arnaud
  • Duinkerken, Gaby
  • Brand-Schaaf, Simone H
  • Peakman, Mark
  • Stangé, Geert
  • Martinson, Laura
  • Kroon, Evert
  • Brandon, Eugene P
  • Pipeleers, Daniel
  • Roep, Bart O
subjects:
  • Adaptive Immunity - immunology
  • Allograft rejection
  • Allografts
  • Antibodies
  • Article
  • asjc
  • atira
  • Autoimmunity
  • Beta cells
  • Cells, Cultured
  • Diabetes
  • Embryonic stem cells
  • embryonic structures
  • Endocrinology
  • Histocompatibility antigens
  • HLA histocompatibility antigens
  • HLA-A2 Antigen
  • Human Embryonic Stem Cells - cytology
  • Human Embryonic Stem Cells - immunology
  • Human Embryonic Stem Cells - metabolism
  • Human Physiology
  • Humans
  • Immunity, Humoral - immunology
  • Immunity, Innate - immunology
  • Insulin-Secreting Cells - cytology
  • Insulin-Secreting Cells - immunology
  • Insulin-Secreting Cells - metabolism
  • Interferon-gamma - metabolism
  • Internal Medicine
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Metabolism
  • pure
  • Stem cells
  • Stem Cells - metabolism
  • subjectarea
  • T cells
  • Transplantation
  • Type 1 diabetes
  • Viral antibodies
ispartof: Diabetologia, 2016-10-27, Vol.60 (1), p.126-133
description: Aims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. Methods We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice. Results We found that hESC-derived pancreatic endodermal cells expressed relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to IFNγ, making these endocrine progenitor cells vulnerable to cytotoxic T cells and alloreactive antibodies. In vivo-differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin-specific T cells killed insulin-producing cells. Conclusions/interpretation hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo-differentiated endocrine cells represent mature targets for adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice.
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleImmunogenicity of human embryonic stem cell-derived beta cells
creatorvan der Torren, Cornelis R ; Zaldumbide, Arnaud ; Duinkerken, Gaby ; Brand-Schaaf, Simone H ; Peakman, Mark ; Stangé, Geert ; Martinson, Laura ; Kroon, Evert ; Brandon, Eugene P ; Pipeleers, Daniel ; Roep, Bart O
creatorcontribvan der Torren, Cornelis R ; Zaldumbide, Arnaud ; Duinkerken, Gaby ; Brand-Schaaf, Simone H ; Peakman, Mark ; Stangé, Geert ; Martinson, Laura ; Kroon, Evert ; Brandon, Eugene P ; Pipeleers, Daniel ; Roep, Bart O
descriptionAims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. Methods We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice. Results We found that hESC-derived pancreatic endodermal cells expressed relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to IFNγ, making these endocrine progenitor cells vulnerable to cytotoxic T cells and alloreactive antibodies. In vivo-differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin-specific T cells killed insulin-producing cells. Conclusions/interpretation hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo-differentiated endocrine cells represent mature targets for adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice.
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languageeng
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subjectAdaptive Immunity - immunology ; Allograft rejection ; Allografts ; Antibodies ; Article ; asjc ; atira ; Autoimmunity ; Beta cells ; Cells, Cultured ; Diabetes ; Embryonic stem cells ; embryonic structures ; Endocrinology ; Histocompatibility antigens ; HLA histocompatibility antigens ; HLA-A2 Antigen ; Human Embryonic Stem Cells - cytology ; Human Embryonic Stem Cells - immunology ; Human Embryonic Stem Cells - metabolism ; Human Physiology ; Humans ; Immunity, Humoral - immunology ; Immunity, Innate - immunology ; Insulin-Secreting Cells - cytology ; Insulin-Secreting Cells - immunology ; Insulin-Secreting Cells - metabolism ; Interferon-gamma - metabolism ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; pure ; Stem cells ; Stem Cells - metabolism ; subjectarea ; T cells ; Transplantation ; Type 1 diabetes ; Viral antibodies
ispartofDiabetologia, 2016-10-27, Vol.60 (1), p.126-133
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1Zaldumbide, Arnaud
2Duinkerken, Gaby
3Brand-Schaaf, Simone H
4Peakman, Mark
5Stangé, Geert
6Martinson, Laura
7Kroon, Evert
8Brandon, Eugene P
9Pipeleers, Daniel
10Roep, Bart O
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descriptionAims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. Methods We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice. Results We found that hESC-derived pancreatic endodermal cells expressed relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to IFNγ, making these endocrine progenitor cells vulnerable to cytotoxic T cells and alloreactive antibodies. In vivo-differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin-specific T cells killed insulin-producing cells. Conclusions/interpretation hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo-differentiated endocrine cells represent mature targets for adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice.
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7Autoimmunity
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10Diabetes
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23Immunity, Innate - immunology
24Insulin-Secreting Cells - cytology
25Insulin-Secreting Cells - immunology
26Insulin-Secreting Cells - metabolism
27Interferon-gamma - metabolism
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30Medicine & Public Health
31Metabolic Diseases
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39Type 1 diabetes
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titleImmunogenicity of human embryonic stem cell-derived beta cells
authorvan der Torren, Cornelis R ; Zaldumbide, Arnaud ; Duinkerken, Gaby ; Brand-Schaaf, Simone H ; Peakman, Mark ; Stangé, Geert ; Martinson, Laura ; Kroon, Evert ; Brandon, Eugene P ; Pipeleers, Daniel ; Roep, Bart O
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3Brand-Schaaf, Simone H
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7Kroon, Evert
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issn0012-186X
eissn1432-0428
abstractAims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. Methods We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice. Results We found that hESC-derived pancreatic endodermal cells expressed relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to IFNγ, making these endocrine progenitor cells vulnerable to cytotoxic T cells and alloreactive antibodies. In vivo-differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin-specific T cells killed insulin-producing cells. Conclusions/interpretation hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo-differentiated endocrine cells represent mature targets for adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice.
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pmid27787618
doi10.1007/s00125-016-4125-y
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