Putative immunogenicity expression profiling using human pluripotent stem cells and derivatives

Stem Cells Transl Med. 2015 Feb;4(2):136-45. doi: 10.5966/sctm.2014-0117. Epub 2015 Jan 9.

Abstract

Autologous human induced pluripotent stem cells (hiPSCs) should allow cellular therapeutics without an associated immune response. This concept has been controversial since the original report that syngeneic mouse iPSCs elicited an immune response after transplantation. However, an investigative analysis of any potential acute immune responses in hiPSCs and their derivatives has yet to be conducted. In the present study, we used correlative gene expression analysis of two putative mouse "immunogenicity" genes, ZG16 and HORMAD1, to assay their human homologous expression levels in human pluripotent stem cells and their derivatives. We found that ZG16 expression is heterogeneous across multiple human embryonic stem cell and hiPSC-derived cell types. Additionally, ectopic expression of ZG16 in antigen-presenting cells is insufficient to trigger a detectable response in a peripheral blood mononuclear cell coculture assay. Neither of the previous immunogenicity-associated genes in the mouse currently appears to be relevant in a human context.

Keywords: HORMAD1; Human embryonic stem cell; Human induced pluripotent stem cell; Immunogenicity; Peripheral blood mononuclear cells; ZG16.

MeSH terms

  • Animals
  • Cell Line
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / immunology*
  • Gene Expression Profiling*
  • Gene Expression Regulation / immunology*
  • Humans
  • Lectins / immunology
  • Membrane Proteins / immunology
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / immunology*
  • Species Specificity

Substances

  • Lectins
  • Membrane Proteins
  • ZG-16 protein, mouse
  • ZG16 protein, human