Bioengineering the human spinal cord

Three dimensional, self-assembled organoids that recapitulate key developmental and organizational events during embryogenesis have proven transformative for the study of human central nervous system (CNS) development, evolution, and disease pathology. Brain organoids have predominated the field, but human pluripotent stem cell (hPSC)-derived models of the spinal cord are on the rise. This has required piecing together the complex interactions between rostrocaudal patterning, which specifies axial diversity, and dorsoventral patterning, which establishes locomotor and somatosensory phenotypes. Here, we review how recent insights into neurodevelopmental biology have driven advancements in spinal organoid research, generating experimental models that have the potential to deepen our understanding of neural circuit development, central pattern generation (CPG), and neurodegenerative disease along the body axis. In addition, we discuss the application of bioengineering strategies to drive spinal tissue morphogenesis in vitro, current limitations, and future perspectives on these emerging model systems.