title: Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors.
abstract: Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients represent a powerful tool for biomedical research and may provide a source for replacement therapies. However, the use of viruses encoding the reprogramming factors represents a major limitation of the current technology since even low vector expression may alter the differentiation potential of the iPSCs or induce malignant transformation. Here, we show that fibroblasts from five patients with idiopathic Parkinson's disease can be efficiently reprogrammed and subsequently differentiated into dopaminergic neurons. Moreover, we derived hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Factor-free hiPSCs maintain a pluripotent state and show a global gene expression profile, more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
authors.affiliation: The Whitehead Institute, Cambridge Center, MA 02142, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Soldner
authors.forename: Dirk
authors.initials: D
authors.lastname: Hockemeyer
authors.forename: Caroline
authors.initials: C
authors.lastname: Beard
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: George W
authors.initials: GW
authors.lastname: Bell
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Cook
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.forename: Alexandra
authors.initials: A
authors.lastname: Blak
authors.forename: Oliver
authors.initials: O
authors.lastname: Cooper
authors.forename: Maisam
authors.initials: M
authors.lastname: Mitalipova
authors.forename: Ole
authors.initials: O
authors.lastname: Isacson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D002454:Cell Differentiation; D065150:Cellular Reprogramming; D004298:Dopamine / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000473:pathology*
chemical_list: D004298:Dopamine