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Differential role of natural killer group 2D in recognition and cytotoxicity of hepatocyte-like cells derived from embryonic stem cells and induced pluripotent stem cells. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Cisneros, T., Dillard, D. W., Qu, X., Arredondo-Guerrero, J., Castro, M., Schaffert, S., Martin, R., Esquivel, C. O., Krams, S. M., Martinez, O. M. 2018

Abstract

Stem cell-based approaches have the potential to address the organ shortage in transplantation. Whereas both embryonic stem cells and induced pluripotent stem cells have been utilized as cellular sources for differentiation and lineage specification, their relative ability to be recognized by immune effector cells is unclear. We determined the expression of immune recognition molecules on hepatocyte-like cells (HLC) generated from murine embryonic stem cells and induced pluripotent stem cells, compared to adult hepatocytes, and we evaluated the impact on recognition by NK cells. We report that HLC lack MHC class I expression, and that embryonic stem cell derived-HLC have higher expression of the NK cell activating ligands Rae1, H60, and Mult1 than induced pluripotent stem cell-derived HLC and adult hepatocytes. Moreover, the lack of MHC class I render embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, susceptible to killing by syngeneic and allogeneic NK cells. Both embryonic stem cell derived-HLC, and induced pluripotent stem cell derived-HLC, are killed by NK cells at higher levels than adult hepatocytes. Finally, we demonstrate that the NK cell activation receptor, NKG2D, plays a key role in NK cell cytotoxicity of embryonic stem cell derived-HLC, but not induced pluripotent stem cell-derived HLC. This article is protected by copyright. All rights reserved.

View details for PubMedID 30549427