Genome-edited safe and immune-evasive human pluripotent cells: Potential solution for allogeneic therapies

We used an embryonic stem cell line (H1) engineered for immune-evading properties to avoid rejection ("AlloAccept") and equipped with a "SafeCell" (SC) kill-switch to eliminate aberrantly proliferating cells. Utilizing a humanized immune system mouse model, we demonstrated the successful generation of allogeneic tissues from SafeCell-AlloAccept (SC-AlloAccept) cells in immunocompetent humanized mice in the immune-active subcutaneous region. These cells formed various tissue types, and their growth can be controlled with pro-drug ganciclovir to activate the kill switch, which eliminated proliferating cells and rendered the remaining tissue dormant. Strikingly, SC-AlloAccept-derived grafts survived for 5 months, underscoring their potential for long-term engraftment. Importantly, neither prior rejection of immunogenic parental H1 cells (sensitization) nor the presence of immune-evasive H1-derived tissue (potential immunocompromising) affected the immune response to a subsequent second transplant. This study validated the utility of SC-AlloAccept human cells in transplantation and enhanced the safety and efficacy of stem cell-based regenerative therapies.