Nature Communications上報告了可提高干細胞療法安全性的一個“清除”程序,。該方法利用一種只在干細胞上表達的細胞表面蛋白從混合細胞類群中將未分化的細胞清除,。
干細胞能發(fā)育成所有類型的細胞，為再生治療帶來極大希望,。然而，通過干細胞的轉(zhuǎn)化所生成的細胞類群也經(jīng)常包含少量未分化的干細胞,，這會引起腫瘤的形成,。
Nissim Benvenisty及其同事發(fā)現(xiàn)，“tight-junction蛋白”Claudin-6只見于人多能干細胞表面上,。他們接著提出基于抗體或一種細菌毒素來識別和殺死表達Claudin-6的細胞的三個不同策略,。這些程序的應(yīng)用能高效地從來自干細胞的混合細胞類群中將表達Claudin-6的細胞清除，并且當將這樣處理過的細胞隨后注射到小鼠體內(nèi)時還能防止腫瘤的形成,。（生物谷Bioon.com）
Nature Communications, doi:10.1038/ncomms2992
Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells
Uri Ben-David,Neta Nudel& Nissim Benvenisty
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.
