The role of the mesenchymal stem cell therapy in bone regeneration of osteoporosis: clinical translation and limitations.

چکیده اصلی

Osteoporosis (OP) is a gradual metabolic bone disease characterized by decreased bone mass and degradation of bone microarchitecture. It affects hundreds of millions of people globally and places considerable pressure on healthcare systems. Current pharmacological treatments, such as bisphosphonates, selective estrogen receptor modulators, and anabolic agents, can reduce fracture risk; however, their prolonged use is limited by significant adverse effects, elevated treatment costs, and a lack of sustained disease remission. Their constraints have intensified interest in restorative approaches utilizing mesenchymal stem cells (MSCs). In the past 20 years, MSCs have emerged as attractive treatment options for OP due to their capacity to differentiate into osteoblasts, modulate immune responses, and exert paracrine effects. Bone marrow-MSCs are the best characterized; nevertheless, MSCs obtained from adipose tissue, umbilical cord, and dental pulp have distinct benefits. Preclinical data demonstrate that direct MSC transplantation enhances bone mineral density, promotes osteoblast production, and reestablishes the equilibrium of bone remodeling in many OP models, including Ovariectomy, glucocorticoid-induced OP, and diabetic OP. Nonetheless, significant obstacles persist: insufficient targeting of osteoporotic bone surfaces, suboptimal cell viability and integration, donor heterogeneity, and unresolved safety concerns. The discovery that the secretome and exosomes (EXOs) produced from MSCs recapitulate several therapeutic advantages of the original cells has initiated a transition toward cell-free methodologies. EXOs produced from MSCs include osteogenic microRNAs (including miR-150-3p and miR-21), inhibit NLRP3 inflammasome activation in osteoclasts, promote macrophage polarization toward an M2 phenotype via TRIM25/TREM1 signaling, and facilitate angiogenesis through the activation of the PI3K/Akt pathway. Furthermore, nanoparticle engineering and combinatorial medicines are advancing to enhance targeting and therapeutic efficacy.

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