Challenges and future perspectives in using mesenchymal stem cells for efficient bone fracture healing.

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.