Strategies for tissue engineering and cell based therapies remain limited by the use of allogeneic cell sources with a requirement for life long immunosuppression. Although autologous iPSC-derived cells have been suggested as an alternative cell source, even these cells may trigger immune rejection due to incomplete reprogramming, the expression of fetal antigens, or acquisition of neoantigens. Further, current fabrication approaches, including additive manufacturing, require months for tissues to fully mature to be sufficiently robust for surgical implantation and the recapitulation of tissue microstructure is often imperfect. Multiplex genome editing offers the potential to reduce alloreactivity and improve the functional characteristics of engineered tissues and cell based therapies. By understanding the role of the immune system, we are investigating genetic pathways that could serve as rational targets to improve the long-term success of organ, tissue, and cell transplantation. We are also developing new additive manufacturing approaches to accelerate organ fabrication with well define tissue architecture.