000165700 001__ 165700
000165700 005__ 20260119151009.0
000165700 0247_ $$2doi$$a10.1007/s12015-011-9248-4
000165700 0248_ $$2sideral$$a67915
000165700 037__ $$aART-2012-67915
000165700 041__ $$aeng
000165700 100__ $$0(orcid)0000-0003-0862-9893$$aConesa, C.
000165700 245__ $$aIdentification of Specific Pluripotent Stem Cell Death-inducing Small Molecules by Chemical Screening.
000165700 260__ $$c2012
000165700 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165700 5203_ $$aA potential application of embryonic and inducible pluripotent stem cells for the therapy of degenerative diseases involves pure somatic cells, free of tumorigenic undifferentiated embryonic and inducible pluripotent stem cells. In complex collections of chemicals with pharmacological potential we expect to find molecules able to induce specific pluripotent stem cell death, which could be used in some cell therapy settings to eliminate undifferentiated cells. Therefore, we have screened a chemical library of 1120 small chemicals to identify compounds that induce specifically apoptotic cell death in undifferentiated mouse embryonic stem cells (ESCs). Interestingly, three compounds currently used as clinically approved drugs, nortriptyline, benzethonium chloride and methylbenzethonium chloride, induced differential effects in cell viability in ESCs versus mouse embryonic fibroblasts (MEFs). Nortriptyline induced apoptotic cell death in MEFs but not in ESCs, whereas benzethonium and methylbenzethonium chloride showed the opposite effect. Nortriptyline, a tricyclic antidepressant, has also been described as a potent inhibitor of mitochondrial permeability transition, one of two major mechanisms involved in mitochondrial membrane permeabilization during apoptosis. Benzethonium chloride and methylbenzethonium chloride are quaternary ammonium salts used as antimicrobial agents with broad spectrum and have also been described as anticancer agents. A similar effect of benzethonium chloride was observed in human induced pluripotent stem cells (hiPSCs) when compared to both primary human skin fibroblasts and an established human fibroblast cell line. Human fibroblasts and hiPSCs were similarly resistant to nortriptyline, although with a different behavior. Our results indicate differential sensitivity of ESCs, hiPSCs and fibroblasts to certain chemical compounds, which might have important applications in the stem cell-based therapy by eliminating undifferentiated pluripotent stem cells from stem cell-derived somatic cells to prevent tumor formation after transplantation for therapy of degenerative diseases.
000165700 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000165700 590__ $$a4.523$$b2012
000165700 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b21 / 118 = 0.178$$c2012$$dQ1$$eT1
000165700 591__ $$aCELL & TISSUE ENGINEERING$$b5 / 16 = 0.312$$c2012$$dQ2$$eT1
000165700 591__ $$aCELL BIOLOGY$$b56 / 183 = 0.306$$c2012$$dQ2$$eT1
000165700 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000165700 700__ $$aDoss, M-X.
000165700 700__ $$aAntzelevitch,C.
000165700 700__ $$aSachinidis, A.
000165700 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza
000165700 700__ $$0(orcid)0000-0003-0062-1029$$aCarrodeguas, J.A.$$uUniversidad de Zaragoza
000165700 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000165700 773__ $$g8, 1 (2012), 116-127$$pStem Cell Rev.$$tSTEM CELL REVIEWS$$x1550-8943
000165700 8564_ $$s476505$$uhttps://zaguan.unizar.es/record/165700/files/texto_completo.pdf$$yPostprint
000165700 8564_ $$s903421$$uhttps://zaguan.unizar.es/record/165700/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000165700 909CO $$ooai:zaguan.unizar.es:165700$$particulos$$pdriver
000165700 951__ $$a2026-01-19-15:09:36
000165700 980__ $$aARTICLE