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    Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cellâ derived neural transplants

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    Authors
    Bieberich, Erhard
    Silva, Jeane
    Wang, Guanghu
    Krishnamurthy, Kannan
    Condie, Brian G.
    Issue Date
    2004-11-22
    URI
    http://hdl.handle.net/10675.2/548
    
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    Abstract
    The formation of stem cellâ derived tumors (teratomas) is observed when engrafting undifferentiated embryonic stem (ES) cells, embryoid bodyâ derived cells (EBCs), or mammalian embryos and is a significant obstacle to stem cell therapy. We show that in tumors formed after engraftment of EBCs into mouse brain, expression of the pluripotency marker Oct-4 colocalized with that of prostate apoptosis response-4 (PAR-4), a protein mediating ceramide-induced apoptosis during neural differentiation of ES cells. We tested the ability of the novel ceramide analogue N-oleoyl serinol (S18) to eliminate mouse and human Oct-4(+)/PAR-4(+) cells and to increase the proportion of nestin(+) neuroprogenitors in EBC-derived cell cultures and grafts. S18-treated EBCs persisted in the hippocampal area and showed neuronal lineage differentiation as indicated by the expression of β-tubulin III. However, untreated cells formed numerous teratomas that contained derivatives of endoderm, mesoderm, and ectoderm. Our results show for the first time that ceramide-induced apoptosis eliminates residual, pluripotent EBCs, prevents teratoma formation, and enriches the EBCs for cells that undergo neural differentiation after transplantation.
    Citation
    J Cell Biol. 2004 Nov 22; 167(4):723-734
    ae974a485f413a2113503eed53cd6c53
    10.1083/jcb.200405144
    Scopus Count
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    Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

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