Title | The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Canham MA, Van Deusen A, Brison DR, De Sousa PA, Downie J, Devito L, Hewitt ZA, Ilic D, Kimber SJ, Moore HD, Murray H, Kunath T |
Journal | Sci Rep |
Volume | 5 |
Pagination | 17258 |
Date Published | 2015 Nov 26 |
ISSN | 2045-2322 |
Keywords | Cell Line, Databases, Genetic, Gene Deletion, Gene Duplication, Human Embryonic Stem Cells, Humans, Karyotyping, Polymorphism, Single Nucleotide |
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. |
DOI | 10.1038/srep17258 |
Alternate Journal | Sci Rep |
PubMed ID | 26607962 |
PubMed Central ID | PMC4660465 |
Grant List | G0700092 / / Medical Research Council / United Kingdom G0801061 / / Medical Research Council / United Kingdom G0801059 / / Medical Research Council / United Kingdom K-1205 / / Parkinson's UK / United Kingdom G0300484 / / Medical Research Council / United Kingdom G0801057 / / Medical Research Council / United Kingdom MR/M017354/1 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom MR/L020335/1 / / Medical Research Council / United Kingdom MR/K017276/1 / / Medical Research Council / United Kingdom MR/L004992/1 / / Medical Research Council / United Kingdom |