Stem Cell-Based Modeling in Pain and ALS

Abstract

Translational research in neurological disorders has largely focused on single or oligo gene rodent models whose value in understanding human disease may be limited. Advances in stem cell technology allow disease modeling using human neurons derived from patients. We have explored the use of derived neuronal cell types in modeling pain and motor neuron disease. In the first case, we use the technique of lineage reprogramming to transdifferentiate human fibroblasts into neurons by Marius Wernig and colleagues. We find that we can derive nociceptor neurons from mouse and human fibroblasts using a group of five transcription factors. We show how the derived nociceptor neurons may be used to model disease pathophysiology with the future goal of performing phenotype-based drug screens. In the second case, we take advantage of existing techniques for differentiating motor neurons from ALS patient iPSCs. We use stem cell modeling to explore physiological differences between ALS and healthy control-derived motor neurons, and we show how iPSC-based phenotypes can be used as platforms to identify and evaluate therapeutic candidates.