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.
| Original language | English |
|---|---|
| Article number | 1992 |
| Journal | Nature Communications |
| Volume | 4 |
| DOIs | |
| State | Published - 2013 |
Bibliographical note
Funding Information:We thank Tamar Golan-Lev for her assistance with graphic design, Dan Lehmann and Bill Breuer for their assistance with cell sorting, and Gal Arad for her assistance with teratoma H&E staining. N.B. is the Herbert Cohn Chair in Cancer Research. U.B.-D. is a Clore Fellow. This work was supported by the Israel Science Foundation (grant no. 269/ 12) and by the Centers of Excellence Legacy Heritage Biomedical Science Partnership (grant no. 1801/10).