The increasing number of elderly people across the globe has led to a rise in osteoporosis and bone fractures, significantly impacting the quality of life and posing substantial health and economic burdens. Despite the development of tissue-engineered bone constructs and stem cell-based therapies to address these challenges, their efficacy is compromised by inadequate vascularization and innervation during bone repair. Innervation plays a pivotal role in tissue regeneration, including bone repair, and various techniques have been developed to fabricate innervated bone scaffolds for clinical use. Incorporating neural-related cells and delivering neurotrophic factors are emerging strategies to accelerate bone regeneration through innervation. However, research into neurogenic cell sources remains limited. Meanwhile, neural stem/progenitor cells (NSPCs) are emerging as promising cells for treating neurodegenerative disorders and spinal cord injuries due to their multifunctional capacity in promoting angiogenesis, neurogenesis, and immunomodulation, making them promising candidates for achieving innervation in bone substitutes. In this review, we discuss the regenerative potential of NSPCs in tissue regeneration. We propose their feasibility for bone therapy through their secreted exosomes during traumatic brain injury, contributing to the acceleration of bone healing. Additionally, we discuss the essential neurotrophic factors released from NSPCs and their osteogenic properties. This review emphasizes the necessity for further investigation of the role of NSPCs in bone regeneration.
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