title: Achilles' heel of pluripotent stem cells: genetic, genomic and epigenetic variations during prolonged culture.
abstract: Pluripotent stem cells differentiate into almost any specialized adult cell type of an organism. PSCs can be derived either from the inner cell mass of a blastocyst-giving rise to embryonic stem cells-or after reprogramming of somatic terminally differentiated cells to obtain ES-like cells, named induced pluripotent stem cells. The potential use of these cells in the clinic, for investigating in vitro early embryonic development or for screening the effects of new drugs or xenobiotics, depends on capability to maintain their genome integrity during prolonged culture and differentiation. Both human and mouse PSCs are prone to genomic and (epi)genetic instability during in vitro culture, a feature that seriously limits their real potential use. Culture-induced variations of specific chromosomes or genes, are almost all unpredictable and, as a whole, differ among independent cell lines. They may arise at different culture passages, suggesting the absence of a safe passage number maintaining genome integrity and rendering the control of genomic stability mandatory since the very early culture passages. The present review highlights the urgency for further studies on the mechanisms involved in determining (epi)genetic and chromosome instability, exploiting the knowledge acquired earlier on other cell types.
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani', Università degli Studi di Pavia, Via Ferrata 9, 27100, Pavia, Italy. paola.rebuzzini@unipv.it.|Center for Health Technologies (C.H.T.), Università degli Studi di Pavia, Via Ferrata 1, Pavia, Italy. paola.rebuzzini@unipv.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Rebuzzini
authors.affiliation: Unita' di Anatomia, Istologia ed Embriologia, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.BI.BI.T.), Università degli Studi di Parma, Via Volturno 39, 43100, Parma, Italy. maurizio.zuccotti@unipr.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zuccotti
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani', Università degli Studi di Pavia, Via Ferrata 9, 27100, Pavia, Italy.|Center for Health Technologies (C.H.T.), Università degli Studi di Pavia, Via Ferrata 1, Pavia, Italy.|Fondazione I.R.C.C.S. Policlinico San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Redi
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie 'Lazzaro Spallanzani', Università degli Studi di Pavia, Via Ferrata 9, 27100, Pavia, Italy. silvia.garagna@unipv.it.|Center for Health Technologies (C.H.T.), Università degli Studi di Pavia, Via Ferrata 1, Pavia, Italy. silvia.garagna@unipv.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Garagna
mesh_terms: D000782:Aneuploidy; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006801:Humans; D053842:Microsatellite Instability; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods
keywords: Aneuploidy; Cell therapy; Embryonic stem cells; Induced pluripotent stem cells; Regenerative medicine; Tissue engineering