title: Establishment and Maintenance of Primary Fibroblast Repositories for Rare Diseases-Friedreich's Ataxia Example.
abstract: Friedreich's ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron of the FXN gene. The number of GAA repeats in FRDA patients varies from approximately 60 to <1000 and is tightly correlated with age of onset and severity of the disease symptoms. The heterogeneity of Friedreich's ataxia stresses the need for a large cohort of patient samples to conduct studies addressing the mechanism of disease pathogenesis or evaluate novel therapeutic candidates. Herein, we report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers. These cells are also a source for generating induced pluripotent stem cell (iPSC) lines by reprogramming, as well as disease-relevant neuronal, cardiac, and pancreatic cells that can then be differentiated from the iPSCs. All FRDA and carrier lines are derived using a standard operating procedure and characterized to confirm mutation status, as well as expression of FXN mRNA and protein. Consideration and significance of creating disease-focused cell line and tissue repositories, especially in the context of rare and heterogeneous disorders, are presented. Although the economic aspect of creating and maintaining such repositories is important, the benefits of easy access to a collection of well-characterized cell lines for the purpose of drug discovery or disease mechanism studies overshadow the associated costs. Importantly, all FRDA fibroblast cell lines collected in our repository are available to the scientific community.
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 Department of Molecular Carcinogenesis, Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center , Smithville, Texas.
authors.forename: Urszula
authors.initials: U
authors.lastname: Polak
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Clark
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Bhalla
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Chen
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Jixue
authors.initials: J
authors.lastname: Li
authors.affiliation: 3 Division of Neurology and Pediatrics, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Farmer
authors.affiliation: 3 Division of Neurology and Pediatrics, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.
authors.forename: Lauren
authors.initials: L
authors.lastname: Seyer
authors.affiliation: 3 Division of Neurology and Pediatrics, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Lynch
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Butler
authors.affiliation: 1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, University of Alabama at Birmingham , Birmingham, Alabama.|4 Department of Molecular Biomedicine, Institute of Bioorganic Chemistry , Polish Academy of Sciences, Poznan, Poland .
authors.forename: Marek
authors.initials: M
authors.lastname: Napierala
mesh_terms: D018070:Biological Specimen Banks; D002454:Cell Differentiation; D002460:Cell Line; D015925:Cryopreservation / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology* / Q000473:pathology; D005621:Friedreich Ataxia / Q000235:genetics / Q000473:pathology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D033862:Iron-Binding Proteins / Q000235:genetics*; D009154:Mutation; D035583:Rare Diseases; D013048:Specimen Handling; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin