title: Chromosomal instability but lack of transformation in human myoblast preparations.
abstract: Genetic alterations have recently been described as emerging during the culture of embryonic stem cells or induced pluripotent stem cells, raising concerns about their safety in future clinical use. Myoblasts are adult stem cells with important therapeutic potential that have been used in clinical trials for almost 20 years, but their genome integrity has not yet been established. Here we produced 10 human myoblast preparations and investigated their genomic stability. At the third passage, half of the preparations had a normal karyotype and half showed one to four alterations/30 metaphases. Chromosome 2 trisomy was found in 1-2/30 metaphases and/or 2/100 nuclei by FISH in 3/10 samples, and there was no other recurrent anomaly. When prolonging cultures, these erratic abnormalities were never associated with a growth advantage. Cellular senescence was manifested in all samples by growth arrest before passage 15. Expression of TERT was always negative. Molecular analysis of individual p53 transcripts did not reveal tumorigenic mutations. CGH array (10 samples) and exome sequencing (one sample) failed to detect copy number variations or accumulation of mutations, respectively. Myoblasts did not grow either in soft agar or in vivo after injection in immunodeficient mice. Hence, occasional genomic abnormalities may occur during myoblast culture but are not associated with risk of transformation.
authors.affiliation: Inserm, U905, Rouen, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bisson
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Corre
authors.forename: Géraldine
authors.initials: G
authors.lastname: Joly-Helas
authors.forename: Pascal
authors.initials: P
authors.lastname: Chambon
authors.forename: Laetitia
authors.initials: L
authors.lastname: Demoulins
authors.forename: Laetitia
authors.initials: L
authors.lastname: Jean
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
authors.forename: Laurent
authors.initials: L
authors.lastname: Drouot
authors.forename: Camille
authors.initials: C
authors.lastname: Giverne
authors.forename: Francis
authors.initials: F
authors.lastname: Roussel
authors.forename: Serge
authors.initials: S
authors.lastname: Jacquot
authors.forename: Christelle
authors.initials: C
authors.lastname: Doucet
authors.forename: Francis
authors.initials: F
authors.lastname: Michot
authors.forename: Marek
authors.initials: M
authors.lastname: Lamacz
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Flaman
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016922:Cellular Senescence; D043171:Chromosomal Instability; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype