Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells

Uri Ben-David, Neta Nudel and Nissim Benvenisty ()
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Uri Ben-David: Stem Cell Unit, Silberman Institute of Life Sciences, The Hebrew University
Neta Nudel: Stem Cell Unit, Silberman Institute of Life Sciences, The Hebrew University
Nissim Benvenisty: Stem Cell Unit, Silberman Institute of Life Sciences, The Hebrew University

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract The tumorigenicity of human pluripotent stem cells is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for human pluripotent stem cell survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed cell populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and Clostridium perfringens enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of human pluripotent stem cell-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated human pluripotent stem cells from culture, highlighting a strategy that may increase the safety of human pluripotent stem cell-based cell therapies.

Date: 2013
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DOI: 10.1038/ncomms2992

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