Tolerance induction to human stem cell transplants with extension to their differentiated progeny.

There is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants diffe...

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Main Authors: Lui, K, Howie, D, Ng, S, Liu, S, Chien, K, Waldmann, H
Format: Journal article
Language:English
Published: 2014
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author Lui, K
Howie, D
Ng, S
Liu, S
Chien, K
Waldmann, H
author_facet Lui, K
Howie, D
Ng, S
Liu, S
Chien, K
Waldmann, H
author_sort Lui, K
collection OXFORD
description There is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants differ from conventional tissue transplants insofar as not all alloantigens are revealed during tolerance induction. This risks that the immune system tolerized to antigens expressed by progenitors may still remain responsive to antigens expressed later during differentiation. Here we show that brief induction with monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and tolerance towards murine ESCs, hESCs, human induced pluripotent stem cells (iPSCs) and hESC-derived progenitors in outbred murine recipients. Tolerance induced to PSC-derived progenitors extends to their differentiated progenies, and sometimes even to different tissues derived from the same donor. Global gene expression profiling identifies clear features in T cells from tolerized grafts that are distinct from those involved in rejection.
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spelling oxford-uuid:2a095974-48cf-45d0-9e47-f9185febd0462022-03-26T12:22:42ZTolerance induction to human stem cell transplants with extension to their differentiated progeny.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2a095974-48cf-45d0-9e47-f9185febd046EnglishSymplectic Elements at Oxford2014Lui, KHowie, DNg, SLiu, SChien, KWaldmann, HThere is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants differ from conventional tissue transplants insofar as not all alloantigens are revealed during tolerance induction. This risks that the immune system tolerized to antigens expressed by progenitors may still remain responsive to antigens expressed later during differentiation. Here we show that brief induction with monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and tolerance towards murine ESCs, hESCs, human induced pluripotent stem cells (iPSCs) and hESC-derived progenitors in outbred murine recipients. Tolerance induced to PSC-derived progenitors extends to their differentiated progenies, and sometimes even to different tissues derived from the same donor. Global gene expression profiling identifies clear features in T cells from tolerized grafts that are distinct from those involved in rejection.
spellingShingle Lui, K
Howie, D
Ng, S
Liu, S
Chien, K
Waldmann, H
Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title_full Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title_fullStr Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title_full_unstemmed Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title_short Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
title_sort tolerance induction to human stem cell transplants with extension to their differentiated progeny
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AT lius toleranceinductiontohumanstemcelltransplantswithextensiontotheirdifferentiatedprogeny
AT chienk toleranceinductiontohumanstemcelltransplantswithextensiontotheirdifferentiatedprogeny
AT waldmannh toleranceinductiontohumanstemcelltransplantswithextensiontotheirdifferentiatedprogeny