Spinal Teratoma to Investigate Cognitive Nerve Dysfunction and GrowthAuthor(s): Afzal Khan
Motor neuron disorders (MNDs) are a heterogeneous group of disorders that affect the brain and/or spinal cord motor neurons (spMN), spinal cord sensory neurons, and the muscular system. Although they have been studied for decades, a comprehensive understanding of the underlying molecular mechanisms is still lacking. Therefore, effective treatments are lacking. Model organisms and relatively simple two-dimensional cell culture systems have contributed significantly to our current knowledge of neuromuscular disease pathogenesis. However, in recent years, 3D human in vitro models have changed the disease modeling landscape. Although cerebral organoids have received the most attention, interest in spinal cord organoids (SCOs) has also increased. Pluripotent stem cell (PSC)-based protocols to generate SpC-like structures, in some cases including adjacent mesoderm and derived skeletal muscle, are constantly being refined and used to study early neuromuscular development and disease in humans. applied. In this review, we outline the development of a human PSC-derived model to generate spMNs and recapitulate SpC development. We also describe how these models have been applied to investigate the basis of human neurological and neurodegenerative diseases. Finally, we outline the main challenges to overcome in order to generate more physiologically relevant human SpC models and propose some exciting new perspectives.