title: Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells.
abstract: As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients' urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery.
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Megan G
authors.initials: MG
authors.lastname: Massa
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gisevius
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hirschberg
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hinz
authors.affiliation: Department of Neuroanatomy, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Department of Neuroanatomy, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Prochnow
authors.affiliation: Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum, Germany.
authors.forename: Aiden
authors.initials: A
authors.lastname: Haghikia
mesh_terms: D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007668:Kidney / Q000166:cytology*; D009103:Multiple Sclerosis / Q000473:pathology*; D014162:Transfection