Stem Cell-Based Regenerative Medicine for Musculoskeletal Disorders

Abstract

Musculoskeletal disorders (MSDs), including osteoarthritis, osteoporosis, intervertebral disc degeneration, tendon and ligament injuries, and muscular dystrophies, represent a major cause of global disability and socioeconomic burden, affecting quality of life and increasing healthcare costs. Conventional treatment modalities, such as physiotherapy, pharmacological interventions, and surgical procedures, are primarily palliative in nature, targeting pain relief and functional support without addressing the underlying mechanisms of tissue degeneration or enabling true structural regeneration. In recent years, stem cell–based regenerative medicine has emerged as a transformative therapeutic strategy capable of restoring musculoskeletal function by promoting tissue repair, modulating immune responses, and facilitating the regeneration of cartilage, bone, tendon, ligament, and muscle tissues. Mesenchymal stem cells (MSCs), owing to their multipotency, paracrine signaling, and immunomodulatory properties, have been most widely explored, demonstrating encouraging preclinical and clinical outcomes in osteoarthritis, bone defects, and tendon healing. Induced pluripotent stem cells (iPSCs) offer additional promise due to their unlimited proliferative capacity and ability to generate patient-specific progenitors, although challenges related to tumorigenicity and genetic stability remain significant hurdles. Tissue-specific progenitors, such as muscle satellite cells and tendon-derived stem/progenitor cells, provide more lineage-committed options with enhanced regenerative efficiency, yet they face difficulties in large-scale expansion and clinical translation. Complementary advances in biomaterials, including hydrogels, nanoscaffolds, and 3D bioprinting technologies, have further enhanced stem cell delivery, survival, and integration into host tissues, while exosome-based, cell-free therapies are emerging as safer alternatives with potent regenerative potential. Despite these advances, critical barriers persist in the form of variable therapeutic outcomes, limited cell engraftment, lack of standardized protocols, and ethical as well as regulatory challenges. Looking ahead, integrating stem cell–based therapies with gene editing, artificial intelligence–driven predictive modeling, and precision medicine frameworks may accelerate clinical translation and establish personalized regenerative strategies for musculoskeletal disorders, and ultimately shifting the paradigm from symptomatic management toward curative interventions.