Human Embryonic Stem Cells and Genomic Instability

Lefort, Nathalie; Perrier, Anselme L.; Laâbi, Yacine; Varela, Christine; Peschanski, Marc

doi:10.2217/rme.09.63

Cited by 42 publications

(34 citation statements)

References 96 publications

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“…The complexity of hES cells is highlighted by the fact that injection of these cells (in their un-transformed state) into immunodeficient mice induced teratoma formation -a practice commonly used as a stringent assay to prove their existence. Indeed, animal embryonic stem cells often displayed genomic abnormalities in culture, which frequently resulted in malignant transformation (Lefort et al 2009;Ben David & Benvenisty, 2011). Similarly, human iPS cells (Takahashi & Yamanaka, 2006), like human ES cells can acquire genetic abnormalities in the culture .…”

Section: Hazardous Pathways Associated With Cellular Dedifferentiatiomentioning

confidence: 99%

Illuminating Hidden Features of Stem Cells

Grafi¹,

Ofir²,

Chalifa‐Caspi³

et al. 2011

Embryonic Stem Cells - Basic Biology to Bioengineering

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Section: Hazardous Pathways Associated With Cellular Dedifferentiatiomentioning

confidence: 99%

Illuminating Hidden Features of Stem Cells

Grafi¹,

Ofir²,

Chalifa‐Caspi³

et al. 2011

Embryonic Stem Cells - Basic Biology to Bioengineering

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“…Since there are approximately 3 Â 10 9 nucleotides per haploid human genome, between 30 and 3000 mutations could occur per cell at each cell cycle (Lefort et al 2009). Fidelity of DNA replication in vitro is likely to be even lower.…”

Section: Extrinsic Factorsmentioning

confidence: 99%

Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells

Stephenson

Ogilvie

Patel

et al. 2010

J. R. Soc. Interface.

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The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources.

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“…The main factors that have been previously proposed to affect the emergence of such aberrations are time in culture (i.e., number of passages), and culture techniques. 9 Thus, Table 1. Schematic representation of the various causes and possible safeguards regarding HiPSC genomic instability…”

mentioning

confidence: 98%