RRC ID 38107
Author Tateno H, Onuma Y, Ito Y, Minoshima F, Saito S, Shimizu M, Aiki Y, Asashima M, Hirabayashi J.
Title Elimination of tumorigenic human pluripotent stem cells by a recombinant lectin-toxin fusion protein.
Journal Stem Cell Reports
Abstract 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.
Volume 4(5)
Pages 811-20
Published 2015-5-12
DOI 10.1016/j.stemcr.2015.02.016
PII S2213-6711(15)00072-7
PMID 25866158
PMC PMC4437484
MeSH ADP Ribose Transferases / genetics ADP Ribose Transferases / metabolism* Bacterial Toxins / genetics Bacterial Toxins / metabolism* Cell Differentiation / drug effects Cell Survival / drug effects Cell Transformation, Neoplastic / drug effects Escherichia coli / metabolism Exotoxins / genetics Exotoxins / metabolism* Humans Lectins / genetics Lectins / metabolism* Plasmids / metabolism Pluripotent Stem Cells / cytology Pluripotent Stem Cells / drug effects Pluripotent Stem Cells / metabolism* Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / isolation & purification Recombinant Fusion Proteins / pharmacology Virulence Factors / genetics Virulence Factors / metabolism*
IF 6.032
Times Cited 54
WOS Category CELL & TISSUE ENGINEERING CELL BIOLOGY
Resource
Human and Animal Cells 253G1(HPS0002) 201B7(HPS0063)