Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells
2016
As
multiple sclerosis researchprogresses, 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 variationsor 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 tubuleepithelial cells were isolated from
multiple sclerosispatients' urine and transfected with pluripotency-inducing episomal factors. Subsequent
induced pluripotent stem cellswere formed into
embryoid bodiesselective 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.
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