Human Leukocyte Antigen Class I and II Knockout Human Induced Pluripotent Stem Cell–Derived Cells: Universal Donor for Cell Therapy

Background We aim to generate a line of “universal donor” human induced pluripotent stem cells (hiPSCs) that are nonimmunogenic and, therefore, can be used to derive cell products suitable for allogeneic transplantation. Methods and Results hiPSCs carrying knockout mutations for 2 key components (β2 microglobulin and class II major histocompatibility class transactivator) of major histocompatibility complexes I and II (ie, human leukocyte antigen [HLA] I/II knockout hiPSCs) were generated using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 9 (Cas9) gene‐editing system and differentiated into cardiomyocytes. Pluripotency‐gene expression and telomerase activity in wild‐type (WT) and HLAI/II knockout hiPSCs, cardiomyocyte marker expression in WT and HLAI/II knockout hiPSC‐derived cardiomyocytes, and assessments of electrophysiological properties (eg, conduction velocity, action‐potential and calcium transient half‐decay times, and calcium transient increase ...