title: Immune potential of allogeneic equine induced pluripotent stem cells.
abstract: BACKGROUND
  Induced pluripotent stem cells (iPSC) have brought immense hope to cellular therapy and regenerative medicine. However, the antigenicity of iPSC has not been well documented and remains a hurdle for clinical applications. Expression of major histocompatibility complex (MHC) molecules by human and murine iPSC is downregulated, making these cells potentially safe for transplantation. No such data are available for any large animal model.
  
  
  OBJECTIVE
  To measure expression of MHC molecules on equine iPSC (eiPSC) and describe their antigenicity using intradermal testing. The hypothesis was that allogeneic eiPSC weakly express MHC molecules and would not elicit a rejection response when injected intradermally.
  
  
  METHODS
  Experimental study involving both in vitro and in vivo components.
  
  
  METHODS
  Two green fluorescent protein-expressing eiPSC lines were analysed by flow cytometry for MHC expression. One line was then transplanted intradermally, along with appropriate controls, into 2 unrelated experimental horses. Blood was collected pre- and 7 days post transplantation. The wheals formed at the sites of injection were measured at regular intervals beginning at 0.25 h until 4 weeks. Tissue samples of the injected sites were obtained at 2, 3, 7 and 30 days post transplantation and analysed by histopathology and immunofluorescence.
  
  
  RESULTS
  Both eiPSC lines weakly expressed MHC molecules. eiPSC were detectable up to 7 days following allogeneic transplantation and elicited no apparent systemic response. Injection of eiPSC caused small wheal formation at the skin surface. Skin sections revealed CD4(+) and CD8(+) mononuclear cells up to 30 days post transplantation.
  
  
  CONCLUSIONS
  These data suggest that while transplantation of allogeneic eiPSC elicits a moderate cellular response, it does not cause acute rejection. The feasibility of banking allogeneic iPSC for regenerative medicine applications should be explored.
authors.affiliation: Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Aguiar
authors.affiliation: Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Theoret
authors.affiliation: Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Smith
authors.affiliation: Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Segura
authors.affiliation: Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Lemire
authors.affiliation: Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: L C
authors.initials: LC
authors.lastname: Smith
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes; D002460:Cell Line; D005260:Female; D006736:Horses; D007271:Injections, Intradermal; D008213:Lymphocyte Activation; D008297:Male; D039904:Pluripotent Stem Cells / Q000276:immunology*; D033581:Stem Cell Transplantation / Q000379:methods / Q000662:veterinary*; D014184:Transplantation, Homologous
keywords: horse; immune response; induced pluripotent stem cells; major histocompatibility complex; regenerative medicine; skin