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

Hdl Handle:
http://hdl.handle.net/10675.2/548
Title:
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
Authors:
Bieberich, Erhard; Silva, Jeane; Wang, Guanghu; Krishnamurthy, Kannan; Condie, Brian G.
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
Issue Date:
22-Nov-2004
URI:
http://hdl.handle.net/10675.2/548
DOI:
10.1083/jcb.200405144
PubMed ID:
15545317
PubMed Central ID:
PMC2172580
Type:
Article
ISSN:
1540-8140
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorBieberich, Erharden_US
dc.contributor.authorSilva, Jeaneen_US
dc.contributor.authorWang, Guanghuen_US
dc.contributor.authorKrishnamurthy, Kannanen_US
dc.contributor.authorCondie, Brian G.en_US
dc.date.accessioned2012-10-26T16:26:37Z-
dc.date.available2012-10-26T16:26:37Z-
dc.date.issued2004-11-22en_US
dc.identifier.citationJ Cell Biol. 2004 Nov 22; 167(4):723-734en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid15545317en_US
dc.identifier.doi10.1083/jcb.200405144en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/548-
dc.description.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 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.en_US
dc.rightsCopyright © 2004, The Rockefeller University Pressen_US
dc.titleSelective 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 transplantsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2172580en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.