Though most hiPSC-derived neurons are grown as monolayers, researchers have developed 3D cultures and brain organoids to produce neuronal ensembles that more closely resemble human brain, e.g., layers of cortex (for review, see Quadrato et al., 2016). These cortico-spheroids typically exhibit a mix of neurons and astrocytes (Paşca et al., 2015), and particularly exciting is the recent description of chimeric organoids, which contain integrated excitatory and inhibitory cortical neurons mimicking interneuron migration observed in vivo (Birey et al., 2017; Mariani et al., 2015; Xiang et al., 2017). Finally, a promising development for drug screening applications lies in the recent creation of a human blood brain barrier (BBB) model from hiPSCs that recapitulates drug BBB permeability in humans (Yamamizu et al., 2017). The inherently different function of rodent and human BBB (Aday et al., 2016) accounts for some of the failed CNS therapeutic trials (Alavijeh et al., 2005) as well as being implicated in neurodegenerative and psychiatric diseases (Desai et al., 2007; Saito and Ihara, 2014). These more complex hiPSC-derived cultures provide an important approach for modeling disease specific circuitry and drug delivery.
