Han Dong, Liu Weiwei, Gong Jinpeng, Ma Yupeng, Sun Zhengwen
Yantaishan Hospital, Trauma Orthopedics, Yantai, China.
Front Bioeng Biotechnol. 2025 May 30;13:1568914. doi: 10.3389/fbioe.2025.1568914. eCollection 2025.
Mesenchymal stem cells (MSCs) demonstrate considerable potential for enhancing bone fracture healing due to their multipotency and immunomodulatory properties. This review investigates the relationship between MSCs, the immune system, and the skeletal microenvironment, focusing on the roles of cytokines and signaling pathways in osteogenesis. The healing process of bone fractures is complex and involves a coordinated response from various cell types, including immune cells and MSCs, which secrete bioactive molecules that promote tissue regeneration and modulate inflammation. Despite their promise, challenges such as variability in MSC sources, ethical considerations, regulatory restrictions, and obstacles in achieving effective delivery and retention at fracture sites restrict their clinical application. Recent advancements in MSC-based therapies, including innovative biomaterials, three-dimensional bioprinting, and gene editing technologies, aim to improve the therapeutic efficacy of MSCs. In addition, strategies to rejuvenate aged MSCs and enhance their regenerative capabilities are critical for addressing age-related fractures, as the functionality of MSCs declines with age. Understanding the mechanisms underlying MSC action, including their paracrine signaling and interaction with the bone microenvironment, is essential for optimizing their therapeutic use. Addressing existing limitations in MSC research and application provides a comprehensive perspective on the future of MSC therapies in bone repair. This review discusses the transformative potential of MSCs in regenerative medicine and orthopedics, highlighting the need for further research to unlock their full capabilities and improve clinical outcomes in patients with bone injuries.
间充质干细胞（MSCs）因其多能性和免疫调节特性，在促进骨折愈合方面展现出巨大潜力。本综述探讨了MSCs、免疫系统和骨骼微环境之间的关系，重点关注细胞因子和信号通路在成骨过程中的作用。骨折愈合过程复杂，涉及多种细胞类型（包括免疫细胞和MSCs）的协同反应，这些细胞分泌促进组织再生和调节炎症的生物活性分子。尽管前景广阔，但MSCs来源的可变性、伦理考量、监管限制以及在骨折部位实现有效递送和留存的障碍等挑战，限制了它们的临床应用。基于MSCs的疗法的最新进展，包括创新生物材料、三维生物打印和基因编辑技术，旨在提高MSCs的治疗效果。此外，使衰老的MSCs恢复活力并增强其再生能力的策略，对于解决与年龄相关的骨折至关重要，因为MSCs的功能会随着年龄增长而下降。了解MSCs作用的潜在机制，包括其旁分泌信号传导以及与骨微环境的相互作用，对于优化其治疗用途至关重要。解决MSCs研究和应用中的现有局限性，为MSCs疗法在骨修复领域的未来发展提供了全面的视角。本综述讨论了MSCs在再生医学和骨科中的变革潜力，强调需要进一步研究以释放其全部能力，并改善骨损伤患者的临床结局。
