Targeted Disruption of the {beta}2-Microglobulin Gene Minimizes the Immunogenicity of Human Embryonic Stem Cells

This study reports the generation of a novel β2-microglobulin (B2M)–/– human embryonic stem cell (hESC) line. Differentiated mature cells from this line do not express cell surface human leukocyte antigen molecules even after interferon- stimulation and are resistant to alloreactive CD8+ T cells. Moreover, this B2M–/– hESC line contains no off-target integration or cleavage events, is devoid of stable B2M mRNA, exhibits a normal karyotype, and retains its self-renewal capacity, genomic stability, and pluripotency. Although B2M–/– hESC-derived cells are more susceptible to natural killer (NK) cells, murine transplantation studies have indicated that they are, overall, much less immunogenic than normal hESCs. Thus, these data show for the first time that, in vivo, the advantages provided by B2M–/– hESC-derived cells in avoiding CD8+ T-cell killing appear significantly greater than any disadvantage caused by increased susceptibility to NK cells.

Source: Stem Cells Translational Medicine - September 17, 2015 Category: Stem Cells Authors: Wang, D., Quan, Y., Yan, Q., Morales, J. E., Wetsel, R. A. Tags: Tissue Engineering and Regenerative Medicine, Embryo Development Source Type: research