Establishment and Validation of a Model for Fetal Neural Ischemia Using Necrotic Core-Free Human Spinal Cord Organoids

Summary: Brain ischemia is a common acute injury caused by impaired blood flow to the brain. Translating effective drug candidates from experimental models to patients has been consistently unsuccessful. However, using human induced pluripotent stem cells (iPSC) provides new opportunities to gain insights into diseases such as brain ischemia. By using a 3D self-assembling iPSC-derived model, researchers were able to characterize the effects of ischemia on neuronal death and impaired neuronal network complexity.

Summary: In vertebrates, the formation of the neural tube during neurulation is crucial for the development of the central nervous system. However, the specific molecular pathways leading to neural tube defects (NTDs) are not well understood. Through the use of human spinal cord organoids (hSCOs), it was discovered that valproic acid (VPA) can cause defects in neurulation. Further analysis revealed significant changes in cell-cell junctional genes/proteins in VPA-treated organoids, and similar gene expression abnormalities and NTD phenotypes were observed in VPA-treated mouse embryos. This study highlights the importance of hSCOs as a valuable resource for studying the molecular mechanisms of human neurulation.