title: The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.
abstract: The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson's, Huntington's, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, UK.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Canham
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Van Deusen
authors.affiliation: Department of Reproductive Medicine, St. Mary's Hospital, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Brison
authors.affiliation: Roslin Cells Limited, Nine Edinburgh BioQuarter, Edinburgh, UK.|Centre for Clinical Brain Sciences and MRC Centre for Regenerative Medicine, The University of Edinburgh, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: De Sousa
authors.affiliation: Roslin Cells Limited, Nine Edinburgh BioQuarter, Edinburgh, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Downie
authors.affiliation: Stem Cell Laboratories, Guy's Assisted Conception Unit, Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors.forename: Liani
authors.initials: L
authors.lastname: Devito
authors.affiliation: Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, UK.
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Hewitt
authors.affiliation: Stem Cell Laboratories, Guy's Assisted Conception Unit, Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors.forename: Dusko
authors.initials: D
authors.lastname: Ilic
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kimber
authors.affiliation: Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, UK.
authors.forename: Harry D
authors.initials: HD
authors.lastname: Moore
authors.affiliation: Roslin Cells Limited, Nine Edinburgh BioQuarter, Edinburgh, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Murray
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, UK.
authors.forename: Tilo
authors.initials: T
authors.lastname: Kunath
mesh_terms: D002460:Cell Line; D030541:Databases, Genetic; D017353:Gene Deletion; D020440:Gene Duplication; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D007621:Karyotyping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics