Nature Communications：利用生物技术清除无用的干细胞

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Nature Communications上报告了可提高干细胞疗法安全性的一个“清除”程序。该方法利用一种只在干细胞上表达的细胞表面蛋白从混合细胞类群中将未分化的细胞清除。# n9 b4 [# {) D& Q

$ c$ U4 M5 A/ _1 J5 `- k干细胞能发育成所有类型的细胞，为再生治疗带来极大希望。然而，通过干细胞的转化所生成的细胞类群也经常包含少量未分化的干细胞，这会引起肿瘤的形成。
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Nissim Benvenisty及其同事发现，“tight-junction蛋白”Claudin-6只见于人多能干细胞表面上。他们接着提出基于抗体或一种细菌毒素来识别和杀死表达Claudin-6的细胞的三个不同策略。这些程序的应用能高效地从来自干细胞的混合细胞类群中将表达Claudin-6的细胞清除，并且当将这样处理过的细胞随后注射到小鼠体内时还能防止肿瘤的形成。6 Q0 g% {  S" Y7 I$ o5 m4 @1 B

  H% U; ?! `3 O5 mNature Communications, doi:10.1038/ncomms2992( T1 m1 ^( h( d3 b& L

! C. r& V, }& x% I% e- D: F9 ^1 EImmunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells3 H7 ^3 D1 D8 q( L3 t6 J
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Uri Ben-David,Neta Nudel& Nissim Benvenisty* X/ {6 O/ R7 K8 a9 \

' h$ P4 Q* h0 k/ F4 O* vThe 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.2 A: ?7 S! t& {9 o