Putative immunogenicity expression profiling using human pluripotent stem cells and derivatives

使用人类多能干细胞及其衍生物进行推定的免疫原性表达分析

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作者:Jason P Awe, Eric H Gschweng, Agustin Vega-Crespo, Jon Voutila, Mary H Williamson, Brian Truong, Donald B Kohn, Noriyuki Kasahara, James A Byrne

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.

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