Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises

Abstract

The systematic generation of neurons from patients with neurological disorders can provide important insights into disease pathology, progression and mechanism. This review will discuss recent progress in modeling neurodegenerative and neurodevelopmental diseases using induced pluripotent stem cells (iPSCs) and highlight some of the current challenges in the field. Combined with other technologies previously used to study brain disease, iPSC modeling has the promise to influence modern medicine on several fronts: early diagnosis, drug development and effective treatment.

Figure 1.

Disease-in-a-dish: using iPSC to model neurological diseases using patients' somatic cells (e.g. skin). Neural progenitors can be generated from iPSC and then give rise to glial cells (oligodendrocytes and astrocytes) and to subtypes of neurons that are relevant for different neurological diseases. Highlighted on this figure are the prospects of using iPSC technology to model for neurological diseases.

Figure 2.

Example of neuronal deficits detected in ASD (RTT) patients. Rett neurons have smaller cell soma size; fewer glutamatergic synapses and altered connectivity when compared with neurons from non-affected (control) individuals. The panel in the middle depicts representative images from dendrites (MAP2) form WT (control) and Rett patient neurons derived from iPSCs. The red puncta (VGLUT1) on the green dendrites represent glutamatergic connections.