Whilst the benefits of iPSC technology are undeniable, there are some limitations in their use for modelling of certain disease states. Such in vitro models have immense power in terms of scalability, and being able to apply techniques such as high throughput genetic or pharmacological screening that would not be possible or be technically difficult in an in vivo setting (Fig. 1). However, they are limited in their ability to recapitulate complex tissue architecture both in terms of the complexity of cell types as well as their spatial organisation, making analysis of many physiological or system-level phenotypes challenging. Highly defined co-culture systems can be beneficial in some situations, for instance where the effects are non-cell autonomous, or rely on cell–cell signalling. This has been successfully applied to modelling of the effects of SOD1 mutation in glial cells on motor neuron survival in cells derived from ALS patients (Di Giorgio et al. 2007, 2008).
