title: Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation deltaF508, using preimplantation genetic diagnosis.
abstract: Human embryonic stem (hES) cells are pluripotent cells isolated from early human embryos. They can be grown in vitro and made to differentiate into many different cell types. These properties have suggested that they may be useful in cell replacement therapy for many degenerative diseases. However, if hES cells could also be manufactured with mutations significant in human disease, they could provide a powerful in-vitro tool for modelling disease processes and progression in a number of different cell types, as well as providing an ideal system for studying in-vitro toxicity and efficacy of drugs and other therapeutic systems such as gene therapy. Embryos with such mutations are generated as part of routine genetic testing during preimplantation genetic diagnosis, providing the opportunity to generate cell lines with significant mutations. A human embryonic stem cell line homozygous for the most common mutation leading to cystic fibrosis in humans (delta F508) has been generated and characterized. This cell line has the same morphology and expresses proteins typical of other unaffected hES cell lines. This cell line represents an important in-vitro tool for understanding the pathophysiology of cystic fibrosis, and presents exciting opportunities to test the efficacy and toxicity of new therapies relevant to CF.
authors.affiliation: Department of Women's Health, GKT School of Medicine, 10th Floor, North Wing, St Thomas' Hospital, London SE1 7EH, UK. susan.pickering@kcl.ac.uk
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Pickering
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Minger
authors.forename: Minal
authors.initials: M
authors.lastname: Patel
authors.forename: Hannah
authors.initials: H
authors.lastname: Taylor
authors.forename: Cheryl
authors.initials: C
authors.lastname: Black
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Burns
authors.forename: Antigoni
authors.initials: A
authors.lastname: Ekonomou
authors.forename: Peter R
authors.initials: PR
authors.lastname: Braude
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D002469:Cell Separation; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D039904:Pluripotent Stem Cells / Q000378:metabolism; D019836:Preimplantation Diagnosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator