Brain repair mechanisms after cell therapy for stroke

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischaemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair.Specifically, we examine how transplanted cell grafts contribute to improved functional recovery either through direct cell replacement or by stimulating endogenous repair pathways. Additionally, we discuss recently implemented preclinical refinement methods, such as preconditioning, microcarriers, genetic safety switches and universal (immune evasive) cell transplants, as well as the therapeutic potential of these pharmacologic and genetic manipulations to further enhance the efficacy and safety of cell therapies.By gaining a deeper understanding of post-ischaemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic. Rust et al. review mechanisms of brain repair after ischaemic stroke, focusing on the potential of stem cells to enhance recovery. They discuss the challenges faced by cell therapies in recent clinical trials and consider how advances in preclinical research might pave the way for next-generation cell therapies.