High‐resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence

The potential use of human mesenchymal stem cells for therapeutic applications implies large scale in vitro culture, increasing the probability of genetic instability and transformation. We examine here the incidence of unbalanced and balanced chromosome rearrangements in polyclonal and single cell‐...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2008-04, Vol.12 (2), p.553-563
Main Authors: Meza‐Zepeda, Leonardo A., Noer, Agate, Dahl, John Arne, Micci, Francesca, Myklebost, Ola, Collas, Philippe
Format: Article
Language:English
Subjects:
adipose stem cell
Adipose tissue
Adipose Tissue - cytology
Adipose Tissue - metabolism
Body fat
Cell culture
Cell cycle
Cells, Cultured
Cellular Senescence - genetics
Chromosome Aberrations
Chromosome Banding
Chromosome rearrangements
Chromosomes
Chromosomes, Human - genetics
Clone Cells - cytology
Cloning
comparative genomic hybridization
DNA - genetics
DNA - isolation & purification
DNA methylation
DNA microarrays
Epigenesis, Genetic
Gene Dosage
Genetic analysis
Genetic transformation
Genomic Instability
Genomics
Humans
Hybridization
Karyotypes
Karyotyping
Liposuction
mesenchymal stem cell
Mesenchymal stem cells
Morphology
Nucleic Acid Amplification Techniques
Nucleic Acid Hybridization
Senescence
Stem cell transplantation
Stem cells
Stem Cells - cytology
Therapeutic applications
Tissue culture
Tissues
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Summary:The potential use of human mesenchymal stem cells for therapeutic applications implies large scale in vitro culture, increasing the probability of genetic instability and transformation. We examine here the incidence of unbalanced and balanced chromosome rearrangements in polyclonal and single cell‐derived cultures of human adipose stem cells to senescence. G‐banding karyotyping of the polyclonal cultures shows a normal karyotype. In addition, high‐resolution microarray‐based comparative genomic hybridization analyses relative to uncultured adipose stem cells from the same donors reveal overall genomic stability in long‐term (∼6 months) polyclonal and clonal culture. One adipose stem cell clone displayed minor deletions in gene‐rich telomeric and sub‐telomeric regions on three chromosomes in early passage. This however, was detected only in a sub‐population of cells that was subsequently spontaneously eliminated from the culture. Apparent pericentromeric instabilities are also occasionally detected in specific chromosomes. Our results indicate that clonal chromosomal aberrations may arise transiently in early passage adipose stem cells (ASC) cultures. Nonetheless, incidence of these aberrations seems to be negligible in the majority of long‐term ASC cultures, at least under the culture conditions used here.
ISSN:1582-1838
1582-4934
DOI:10.1111/j.1582-4934.2007.00146.x