Curcumin enhances the protective effect of bone marrow mesenchymal stem cell-derived extracellular vesicles in alleviating intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, with limited treatment options. Bone marrow mesenchymal stem cell-derived extracellular vesicles (BM-MSC-EVs, EVs) have shown potential in regenerative therapies. This study aimed to evaluate the therapeutic effects of curcumin-loaded BM-MSC-EVs (BM-MSC-EVs-Cur, EVs-Cur) in a rat model of IVDD. METHOD: First, we characterized BM-MSCs and used them to produce EVs. Curcumin was encapsulated into these EVs. Subsequently, a surgical IVDD rat model was established, and animals were treated with curcumin, EVs, or EVs-Cur. Histological, biochemical, and molecular analyses were performed to assess disc cartilage integrity, chondrogenesis, oxidative stress, cell proliferation/apoptosis, and PI3K-AKT-mTOR pathway levels. RESULTS: We found that EVs-Cur treatment significantly improved disc cartilage integrity and enhanced chondrogenesis. EVs-Cur also reduced oxidative stress by restoring antioxidant markers and attenuated the phosphorylation of PI3K/AKT/mTOR signaling, thereby modulating the expression of apoptosis-related proteins (Bax, Bcl2, cleaved-caspase-3 and Pro-caspase-3). Furthermore, EVs-Cur exhibited superior effects in promoting cell proliferation and reducing apoptosis than curcumin or EVs alone. CONCLUSIONS: In the present work, EVs-Cur was found to be effective in alleviating IVDD by reducing oxidative stress, restoring cartilage integrity, and inhibiting the PI3K/AKT/mTOR pathway. These findings highlight EVs-Cur as a promising cell-free therapeutic strategy for IVDD.