title: Beneath the sword of Damocles: regenerative medicine and the shadow of immunogenicity.
abstract: Few topics in regenerative medicine have inspired such impassioned debate as the immunogenicity of cell types and tissues differentiated from pluripotent stem cells. While early predictions suggested that tissues derived from allogeneic sources may evade immune surveillance altogether, the pendulum has since swung to the opposite extreme, with reports that the ectopic expression of a few developmental antigens may prompt rejection, even of tissues differentiated from autologous cell lines. Here we review the evidence on which these contradictory claims are based in order to reach an objective assessment of the likely magnitude of the immunological challenges ahead. Furthermore, we discuss how the inherent properties of pluripotent stem cells may inform strategies for reducing the impact of immunogenicity on the future ambitions of regenerative medicine.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fairchild
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Horton
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Priyoshi
authors.initials: P
authors.lastname: Lahiri
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Kumaran
authors.initials: K
authors.lastname: Shanmugarajah
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davies
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology*; D044968:Regenerative Medicine
keywords: allograft rejection; embryonic stem cells; haplobank; immune suppression; induced pluripotent stem cells; regulatory T cell; transplantation tolerance