Use of the NeoThy is important for PSC immunogenicity studies, as other humanized mouse models besides the NeoThy and BLT lack human thymus incorporation and are suboptimal for assessing human MHC-restricted T cell responses. pubmed.ncbi.nlm.nih.gov/32588980/ pubmed.ncbi.nlm.nih.gov/37386161/

We transplanted ICAM-1 KO into next-generation NeoThy humanized mice and saw that the KO cells were retained, but wild type cells were dramatically reduced in size, indicating that the KOs are protected against allograft rejection in vivo.

ICAM-1 KO reduced binding of adaptive (e.g., T cells) and innate (e.g., neutrophils) immune cells. It also resulted in markedly diminished T cell activation and proliferation in vitro.

We successfully and reproducibly made three ICAM-1 knock out cardiovascular cell types (endothelial cells, cardiomyocytes, and cardiac fibroblasts) from multiple PSC lines, including induced PSCs and embryonic stem cells.

ICAM-1 is expressed on endothelial and other cells and is upregulated in response to post-transplantation inflammatory stimuli (e.g., TNFa, IFNg). There are cell surface and secreted forms of ICAM-1. Our KO prevented both types of protein from being expressed by the cells.