Iyer Nisha R, Ashton Randolph S
Department of Biomedical Engineering, Tufts University, Medford, MA, United States.
Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, United States.
Front Cell Dev Biol. 2022 Aug 26;10:942742. doi: 10.3389/fcell.2022.942742. eCollection 2022.
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 , current limitations, and future perspectives on these emerging model systems.
三维自组装类器官能够重现胚胎发育过程中的关键发育和组织事件，这已被证明对人类中枢神经系统（CNS）发育、进化及疾病病理学研究具有变革性意义。脑类器官在该领域占据主导地位，但源自人类多能干细胞（hPSC）的脊髓模型正在兴起。这就需要梳理前后轴模式（决定轴向多样性）与背腹轴模式（确立运动和躯体感觉表型）之间的复杂相互作用。在此，我们回顾了神经发育生物学的最新见解如何推动脊髓类器官研究的进展，生成了一些实验模型，这些模型有可能加深我们对沿身体轴线的神经回路发育、中枢模式发生器（CPG）及神经退行性疾病的理解。此外，我们还讨论了生物工程策略在驱动脊髓组织形态发生方面的应用、当前的局限性以及这些新兴模型系统的未来前景。
