中枢神经系统发育
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Nature子刊:同济大学朱融融/程黎明团队构建新型脊髓类器官,可修复脊髓损伤并恢复运动能力
生物世界· 2025-10-27 04:23
Core Insights - The article discusses the development of engineered thoracic spinal cord organoids (enTsOrg) for potential therapeutic applications in spinal cord injury (SCI) repair, showcasing their ability to restore motor function in paralyzed mice [2][3][11] Group 1: Research Findings - The research team successfully constructed enTsOrg that mimics the heterogeneity and mature neural circuit structure of the thoracic spinal cord, leading to the reorganization of neural circuits and recovery of hind limb motor function in mice with complete spinal cord injury [3][10] - The study highlights the complexity of the central nervous system's development and opens potential pathways for designing organoids tailored for specific anatomical regions in neural injury treatment [4][11] Group 2: Methodology - The engineered organoids were created using induced pluripotent stem cells (iPSCs) derived from fibroblasts and layered double hydroxide (LDH) matrices within a basement membrane hydrogel, successfully reproducing the diverse neuronal distribution and electrophysiological characteristics similar to natural spinal cord tissue [7][9] - The transplantation of enTsOrg into a mouse model of thoracic complete spinal cord injury resulted in significant improvements in motor function, neuronal subtype diversity, and electrophysiological conduction of motor neurons compared to non-segment-specific spinal cord organoids [9][10] Group 3: Mechanisms of Action - LDH promotes the formation of region-specific thoracic spinal cord organoids by activating PTCH1 protein and regulating retinoic acid signaling pathways, enhancing neuronal survival and promoting the differentiation and maturation of motor neurons and interneurons [9][10] - The study indicates that the transplanted enTsOrg formed more refined functional neurons with dorsal and ventral characteristics, crucial for muscle contraction and extension in paralyzed animals [9][10]