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
MetadataShow full item record
AbstractThe 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 Î²-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.
CitationJ Cell Biol. 2004 Nov 22; 167(4):723-734
- Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation.
- Authors: Chung S, Shin BS, Hedlund E, Pruszak J, Ferree A, Kang UJ, Isacson O, Kim KS
- Issue date: 2006 Jun
- Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide.
- Authors: Bieberich E, MacKinnon S, Silva J, Noggle S, Condie BG
- Issue date: 2003 Aug 4
- Propagation of undifferentiated human embryonic stem cells with nano-liposomal ceramide.
- Authors: Salli U, Fox TE, Carkaci-Salli N, Sharma A, Robertson GP, Kester M, Vrana KE
- Issue date: 2009 Jan-Feb
- Regulation of neural progenitor cell motility by ceramide and potential implications for mouse brain development.
- Authors: Wang G, Krishnamurthy K, Chiang YW, Dasgupta S, Bieberich E
- Issue date: 2008 Jul
- De-differentiation of mouse interfollicular keratinocytes by the embryonic transcription factor Oct-4.
- Authors: Grinnell KL, Yang B, Eckert RL, Bickenbach JR
- Issue date: 2007 Feb