Convergence of human cellular models and genetics to study neural stem cell signaling to enhance central nervous system regeneration and repair.

Human central nervous system (CNS) regeneration is considered the holy grail of neuroscience research, and is one of the most pressing and difficult questions in biology and science. Despite more than 20 years of work in the field of neural stem cells (NSCs), the area remains in its infancy as our understanding of the fundamental mechanisms that can be leveraged to improve CNS regeneration in neurological diseases is still growing. Here, we focus on the recent lessons from lower organism CNS regeneration genetics and how such findings are starting to illuminate our understanding of NSC signaling pathways in humans. These findings will allow us to improve upon our knowledge of endogenous NSC function, the utility of exogenous NSCs, and the limitations of NSCs as therapeutic vehicles for providing relief from devastating human neurological diseases. We also discuss the limitations of activating NSC signaling for CNS repair in humans, especially the potential for tumor formation. Finally, we will review the recent advances in new culture techniques, including patient-derived cells and cerebral organoids to model the genetic regulation of signaling pathways controlling the function of NSCs during injury and disease states.