Elimination of tumorigenic human pluripotent stem cells by a recombinant lectin-toxin fusion protein.
Elimination of tumorigenic human pluripotent stem cells by a recombinant lectin-toxin fusion protein.
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DOI：
10.1016/j.stemcr.2015.02.016
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发表时间：
2015-05-12
影响因子：
5.9
通讯作者：
Hirabayashi, Jun
中科院分区：
文献类型：
--
作者：
Tateno, Hiroaki;Onuma, Yasuko;Ito, Yuzuru;Minoshima, Fumi;Saito, Sayoko;Shimizu, Madoka;Aiki, Yasuhiko;Asashima, Makoto;Hirabayashi, Jun
基于干细胞的疗法在再生医学中的应用受到残留的人类多能干细胞的致瘤潜力的阻碍。此前，我们通过使用高密度凝集素微阵列进行全面的糖类分析，确定了一种人类多能干细胞特异性凝集素探针，称为rBC2LCN。我们构建了含有铜绿假单胞菌外毒素A催化结构域的重组凝集素-毒素融合蛋白rBC2LCN-PE23，该融合蛋白可在大肠杆菌中以可溶性形式表达，并经一步亲和层析纯化为均一。RBC2LCN-PE23与人类多能干细胞结合，然后内化，允许细胞内运送一批细胞毒蛋白。在培养液中加入rBC2LCN-PE23足以完全消除人多能干细胞。因此，rBC2LCN-PE23有可能对基于干细胞的治疗的安全性做出贡献。RBC2LCN-PE23与人多能干细胞结合并被人多能干细胞内化rBC2LCN-PE23消除了人多能干细胞，但未分化细胞rBC2LCN-PE23应有助于干细胞治疗的安全性。在这篇文章中，Tateno和他的同事提出了一种方法，使用名为rBC2LCN-PE23的重组凝集素-毒素融合蛋白从混合细胞群中消除致瘤的人类多能干细胞。
The application of stem-cell-based therapies in regenerative medicine is hindered by the tumorigenic potential of residual human pluripotent stem cells. Previously, we identified a human pluripotent stem-cell-specific lectin probe, called rBC2LCN, by comprehensive glycome analysis using high-density lectin microarrays. Here we developed a recombinant lectin-toxin fusion protein of rBC2LCN with a catalytic domain of Pseudomonas aeruginosa exotoxin A, termed rBC2LCN-PE23, which could be expressed as a soluble form from the cytoplasm of Escherichia coli and purified to homogeneity by one-step affinity chromatography. rBC2LCN-PE23 bound to human pluripotent stem cells, followed by its internalization, allowing intracellular delivery of a cargo of cytotoxic protein. The addition of rBC2LCN-PE23 to the culture medium was sufficient to completely eliminate human pluripotent stem cells. Thus, rBC2LCN-PE23 has the potential to contribute to the safety of stem-cell-based therapies. rBC2LCN-PE23 binds to and is internalized by human pluripotent stem cells rBC2LCN-PE23 eliminates human pluripotent stem cells, but not differentiated cells rBC2LCN-PE23 should contribute to the safety of stem-cell-based therapies The application of human pluripotent stem cells in regenerative medicine is hindered by the tumorigenic risk from residual human pluripotent stem cells. In this article, Tateno and colleagues present a method to eliminate tumorigenic human pluripotent stem cells from a mixed cell population using a recombinant lectin-toxin fusion protein, termed rBC2LCN-PE23.
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影响因子：
3.7
作者：
Richards M;Phoon CW;Goh GT;Seng EK;Guo XM;Tan CM;Chan WK;Lee JM
通讯作者：
Lee JM
影响因子：
2.9
作者：
Dam, Tarun K.;Gerken, Thomas A.;Brewer, C. Fred
通讯作者：
Brewer, C. Fred
影响因子：
3.7
作者：
Gropp M;Shilo V;Vainer G;Gov M;Gil Y;Khaner H;Matzrafi L;Idelson M;Kopolovic J;Zak NB;Reubinoff BE
通讯作者：
Reubinoff BE
影响因子：
5.2
作者：
Choo, Andre B.;Tan, Heng Liang;Yap, Miranda
通讯作者：
Yap, Miranda
DOI：
10.1073/pnas.1321126111
发表时间：
2014-06-10
影响因子：
11.1
作者：
King, Chris;Garza, Esteban N.;Baker, David
通讯作者：
Baker, David