Our inability to derive the neuronal diversity that comprises the posterior central nervous system (pCNS) using human pluripotent stem cells (hPSCs) poses an impediment to understanding human neurodevelopment and disease in the hindbrain and spinal cord.
The spinal cord contains billions of neurons, with a huge diversity of subtypes enabling sensory, proprioceptive, and motor function. However, current human stem cell-based in vitro models and prospective cell transplantation therapies fail to reflect the significant regional specificity of spinal cells.
In tissue engineering applications, sacrificial molding of hydrogel monoliths is a versatile technique for creating 3D molds to control tissue morphology. Previous sacrificial templates fabricated by serial processes such as solvent casting and thermal extrusion/fiber drawing can be used to effectively mold internal geometries within rapidly polymerizing, bulk curing hydrogels.
Transplantation of human pluripotent stem cell (hPSC)-derived neurons into chick embryos is an established preliminary assay to evaluate engraftment potential. Yet, with recent advances in deriving diverse human neuronal subtypes, optimizing and standardizing such transplantation methodology for specific subtypes at their correlated anatomical sites is still required.
Human pluripotent stem cell-derived neural organoids provide unprecedented potential to recapitulate human brain and spinal cord tissues in vitro. However, organoid morphogenesis relies upon cell-intrinsic self-assembly of biomimetic tissue structures in the absence of normal developmental constraints and morphogen signaling centers.