Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders

• Published in: Frontiers in molecular neuroscience Vol. 9; p. 78
• Main Authors: Barral, Serena, Kurian, Manju A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 06.09.2016; Frontiers Media S.A
• Subjects: Age; Cell differentiation; Central nervous system; Central nervous system diseases; Children; Disease; Dopamine receptors; Fetuses; Fibroblasts; Gene therapy; Inhibitory postsynaptic potentials; Motor neurons; Mutation; Neurological diseases; Neurological disorders; Neuroscience; Patients; Phenotypes; Pluripotency; Stem cells; γ-Aminobutyric acid; United Kingdom > UK; in vitro disease modeling; childhood neurological disorders; iPSCs; drug screening; gene therapies; isogenic control
• DOI: 10.3389/fnmol.2016.00078
• ISSN: 1662-5099

The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders.