Putative immunogenicity expression profiling using human pluripotent stem cells and derivatives

Area of Science:

• Stem cell biology
• Immunology
• Regenerative medicine

Background:

• Autologous human induced pluripotent stem cells (hiPSCs) are promising for cell therapeutics due to their potential to avoid immune rejection.
• Previous studies in mice suggested that syngeneic iPSCs could elicit an immune response, creating controversy regarding the safety of hiPSC-based therapies.
• A thorough investigation into potential acute immune responses associated with hiPSCs and their derivatives has been lacking.

Purpose of the Study:

• To investigate the potential immunogenicity of human induced pluripotent stem cells (hiPSCs) and their derivatives.
• To assess the relevance of mouse immunogenicity genes (ZG16 and HORMAD1) in a human context.
• To determine if hiPSC-derived cells trigger an immune response in humans.

Main Methods:

• Correlative gene expression analysis of human homologous genes (ZG16 and HORMAD1) in human pluripotent stem cells and their derivatives.
• Assessing ZG16 expression levels across various human embryonic stem cell and hiPSC-derived cell types.
• Evaluating the immunogenic potential of ectopic ZG16 expression in antigen-presenting cells using a peripheral blood mononuclear cell coculture assay.

Main Results:

• ZG16 gene expression was found to be heterogeneous across different human embryonic stem cell and hiPSC-derived cell types.
• Ectopic expression of ZG16 in antigen-presenting cells did not induce a detectable immune response in peripheral blood mononuclear cell coculture assays.
• The two previously identified mouse immunogenicity genes, ZG16 and HORMAD1, do not appear to be relevant in the context of human stem cell immunogenicity.

Conclusions:

• The investigated mouse immunogenicity genes (ZG16 and HORMAD1) are not relevant for assessing the immunogenicity of human induced pluripotent stem cells (hiPSCs).
• Human induced pluripotent stem cells and their derivatives are unlikely to elicit an acute immune response based on these specific gene markers.
• These findings support the potential of autologous hiPSCs for safe and effective cellular therapeutics without immune complications.