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      Advances in reprogramming-based study of neurologic disorders.

      1 , 1

      Stem cells and development

      Mary Ann Liebert Inc

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          Abstract

          The technology to convert adult human non-neural cells into neural lineages, through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer, and direct lineage reprogramming or transdifferentiation has progressed tremendously in recent years. Reprogramming-based approaches aimed at manipulating cellular identity have enormous potential for disease modeling, high-throughput drug screening, cell therapy, and personalized medicine. Human iPSC (hiPSC)-based cellular disease models have provided proof of principle evidence of the validity of this system. However, several challenges remain before patient-specific neurons produced by reprogramming can provide reliable insights into disease mechanisms or be efficiently applied to drug discovery and transplantation therapy. This review will first discuss limitations of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology. Specifically, we will address issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two-dimensional differentiation paradigms. Second, we will assess recent progress and the future prospects of reprogramming-based neurologic disease modeling. This includes three-dimensional disease modeling, advances in reprogramming technology, prescreening of hiPSCs and creating isogenic disease models using gene editing.

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          Author and article information

          Journal
          Stem Cells Dev.
          Stem cells and development
          Mary Ann Liebert Inc
          1557-8534
          1547-3287
          Jun 01 2015
          : 24
          : 11
          Affiliations
          [1 ] Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California.
          Article
          10.1089/scd.2015.0044
          4440984
          25749371

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