title: Mesenchymal derivatives of genetically unstable human embryonic stem cells are maintained unstable but undergo senescence in culture as do bone marrow-derived mesenchymal stem cells.
abstract: Recurrent chromosomal alterations have been repeatedly reported in cultured human embryonic stem cells (hESCs). The effects of these alterations on the capability of pluripotent cells to differentiate and on growth potential of their specific differentiated derivatives remain unclear. Here, we report that the hESC lines HUES-7 and -9 carrying multiple chromosomal alterations produce in vitro mesenchymal stem cells (MSCs) that show progressive growth arrest and enter senescence after 15 and 16 passages, respectively. There was no difference in their proliferative potential when compared with bone marrow-derived MSCs. Array comparative genomic hybridization analysis (aCGH) of hESCs and their mesenchymal derivatives revealed no significant differences in chromosomal alterations, suggesting that genetically altered hESCs are not selected out during differentiation. Our findings indicate that genetically unstable hESCs maintain their capacity to differentiate in vitro into MSCs, which exhibit an in vitro growth pattern of normal MSCs and not that of transformed cells.
authors.affiliation: 1 Stem Cell Transplant Unit, Aghia Sophia Children's Hospital , Thivon and Papadiamantopoulou, 11527, Athens, Greece .
authors.forename: Angeliki
authors.initials: A
authors.lastname: Karagiannidou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Varela
authors.forename: Krinio
authors.initials: K
authors.lastname: Giannikou
authors.forename: Maria
authors.initials: M
authors.lastname: Tzetis
authors.forename: Antonia
authors.initials: A
authors.lastname: Spyropoulos
authors.forename: George
authors.initials: G
authors.lastname: Paterakis
authors.forename: Eftichia
authors.initials: E
authors.lastname: Petrakou
authors.forename: Maria
authors.initials: M
authors.lastname: Theodosaki
authors.forename: Evgenios
authors.initials: E
authors.lastname: Goussetis
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D002648:Child; D055028:Comparative Genomic Hybridization; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*