Humanized Mouse Models for Evaluation of PSC Immunogenicity

New human pluripotent stem cell (hPSC)‐derived therapies are advancing to clinical trials at an increasingly rapid pace. In addition to ensuring that the therapies function properly, there is a critical need to investigate the human immune response to these cell products. A robust allogeneic (or autologous) immune response could swiftly eliminate an otherwise promising cell therapy, even in immunosuppressed patients. In coming years, researchers in the regenerative medicine field will need to utilize a number of in vitro and in vivo assays and models to evaluate and better understand hPSC immunogenicity. Humanized mouse models—mice engrafted with functional human immune cell types—are an important research tool for investigating the mechanisms of the adaptive immune response to hPSC therapies. This article provides an overview of humanized mouse models relevant to the study of hPSC immunogenicity and explores central considerations for investigators seeking to utilize these powerful models in their research. © 2020 Wiley Periodicals LLC.