Rewiring the ischaemic brain with human-induced pluripotent stem cell-derived cortical neurons

Successful translation into the clinic of experimental molecular therapies for stroke has been limited so far, with the single exception of recombinant tissue plasminogen activator (Wahlgren et al. , 2007). This frustrating and rather distressing situation has in part been alleviated by the degree of spontaneous recovery that occurs in the majority of stroke survivors (Schaechter, 2004). Nonetheless, up to one-third of stroke patients remain permanently disabled and require definitive placement either in a nursing home or an assisted living environment, with great economic and social consequences (Lloyd-Jones et al. , 2009).Recent advances in stem cell biology have raised expectations that diseases and injuries of the CNS may be ameliorated by the delivery of non-haematopoietic stem cell-based therapeutics. Within this context, the local versus systemic transplantation of neural stem cells has emerged as a recovery-promoting approach in preclinical models of neurological disorders, including experimental stroke (Bacigaluppi et al. , 2008; Martino et al. , 2011). Neural stem cells possess properties distinct from those of conventional therapeutics that extend far beyond the regenerative-medicine arena. Part drug and part device, transplanted neural stem cells sense diverse signals, migrate to specific sites in the body, integrate inputs to make decisions, and execute complex response behaviours, all in the context of specific tissue environments (Fischbach et al. , 2013).Chronic and invalidating neurological diseases have become the ideal candidates for translating functionally flexible stem cells into clinically relevant medicines. For stroke patients, the prolonged interval between the acute onset and a delayed stem cell transplant allows the disease to stabilize, avoids first line complications and permits some degree of spontaneous recovery. A novel frontier of stem cell medicine is now arising, …