Regenerative Potential of Neural Stem/Progenitor Cells for Bone Repair

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. Impact Statement Innervation has gained attention in bone tissue engineering, with nerve-related cells shown to promote bone regeneration. However, few previous reviews have examined the potential of neurogenic cells, particularly neural stem/progenitor cells, for bone repair. This review explores the feasibility of these cells in enhancing bone regeneration, discussing roles in angiogenesis, immune regulation, neurogenesis, and osteogenesis. The effects of these cells under traumatic brain injury and their neurotrophic factors on bone repair are also reviewed. Finally, the impact of secreted factors from neural progenitor cells on osteogenic differentiation is examined, highlighting their potential as a novel cell source for bone repair.