Research Progress on the Mechanisms of Endogenous Neural Stem Cell Differentiation in Spinal Cord Injury Repair

Tianwei Wang¹Qing Han²Shi Lv¹Li-ping Zhang¹Hengrui Li¹Jian Liu¹Jinyi Kuang¹Bao-liang Sun¹SUN JINGYI^3*

• ¹Shandong First Medical University, Tai'an, Shandong, China
• ²College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
• ³Shandong Provincial Hospital, Jinan, Shandong Province, China

Spinal cord injury (SCI) is a devastating condition with limited self-repair capacity, resulting in long-term disabilities. Endogenous neural stem cells (eNSCs), which are present in the adult central nervous system, (CNS), hold significant potential for repairing neural damage following SCI. These cells have the ability tocan proliferate, migrate to the injury site, and differentiate into various neural cell types, including neurons and glial cells. However, after SCI, eNSCs predominantly differentiate into astrocytes, 样式定义: EndNote Bibliography: 字体: (默认) 等 线, (中文) 等线 with minimal neuronal differentiation, thereby hindering effective neural regeneration. This review summarizes the key mechanisms underlying the differentiation of eNSCs into neurons, focusing on the molecular signaling pathways that regulate their fate, including the Notch, Wnt/β-catenin, Sonic Hedgehog, and PI3K/Akt pathways. Additionally, it It also discusses the microenvironment's role of the microenvironment, including factors such as hypoxia, extracellular matrix components, and inflammatory cytokines, which influence eNSCeNSCs differentiation. The review also highlights potential therapeutic strategies aimed at enhancing eNSCto enhance eNSCs differentiation into neurons, including the use of biomaterials and multimodal approaches that combine pharmacological, physical, and tissue-engineering techniques. Despite progress in understanding eNSCeNSCs biology and signaling mechanisms, challenges remain in optimizing therapeutic strategies for SCI repair. Future research should focus on overcoming these limitations, with an emphasis onemphasizing refining treatment timing, drug delivery systems, and the development of personalized therapies to promote effective neural regeneration and functional recovery after SCI.SCI is a severe neurological condition that leads to the loss of motor, autonomic, and sensory functions below the site of injury site (Li et al., 2024a). SCI disrupts the central nervous system (CNS),, interrupts neural