Functional recovery through the plastic adaptation of organoid grafts in cortical tissue

The lack of effective therapeutic options for patients suffering from neurological impairments related to acquired brain damage requires novel translational strategies, among which transplantation of neural tissue is receiving strong attention. One of the most recent developments involves the implantation of brain organoid models, derived from embryonic or induced pluripotent stem cells, into damaged rodent cortices. While this approach is gaining popularity, the extent of graft integration within the host tissue remains poorly understood. This review aims to examine whether xenotransplanting organoids into cortical tissue induces functional recovery and plastic adaptation to the damaged implantation sites. Physiological indications of grafted organoid plasticity and integration into the host included viability, corticogenesis, vascularisation, growth, and the development of area-specific morphological identities. The functional integration into host neural circuitry has been probed by tracing of axonal projection growth according to implantation sites, but also through observations of spontaneous, stimulus evoked, and selectively tuned activity of grafted neurons. Finally, some studies also investigated whether the engraftment procedure facilitated behavioural recovery in tasks requiring motor, memory, or reward-seeking functions. Overall, organoid grafts show signs of progressive anatomical, functional, and behaviourally-relevant integration within the damaged host cortices. Yet, further investigation is necessary before this transplantation approach can be actually translated into a robust method to achieve functional restoration in patients suffering from brain damage.