By editing out a set of proteins on the surface of human pluripotent stem cells, researchers have ensured they will be not be rejected by the body’s immune system.
Researchers have reported how they genetically edited out a key set of proteins found on the surface of human pluripotent stem cells (hPSCs) that are the targets of immune rejection, rendering them invisible to the body’s immune system.
The multi-institutional research team was led by Dr Xiaoqing Zhang and Dr Lin Ma from the Tongji University School of Medicine, China.
“What we have done is taken advantage of the non-classical human leukocyte antigen (HLA) molecules, which encode the main targets of allograft rejection, to construct hypoimmunogenic hPSCs,” Zhang said. “Our strategy not only ameliorates the body’s main immune-rejection weapons — T cells (especially CD8+ Ts), natural killer (NK) cells and antigen-presenting cells – but also attenuates cell contact-triggered cell killing and immunogenicity of the allograft environment.”
The team say their work grew out of their knowledge that the HLA-G family is one of the most prominently expressed HLA class I molecules in the placenta, with the job of protecting foetal tissue from the mother’s immune system.
“It’s a remarkable example of immune accommodation in mammals,” Zhang explained. “So we engineered hPSCs using CRISPR-Cas9 gene-editing technology for beta-2 microglobulin (β2m) knock out or for biallelic knock-in of HLA-G1 within the endogenous