Cell-Free Fat Extract for the Treatment of Lumbar Disc Degeneration: A Novel Approach Using Adipose-Derived Biologic.

Background: Intervertebral disc degeneration (IVDD) is a major cause of chronic back pain. Recent studies suggest that ferroptosis, a form of cell death, contributes to the degeneration of nucleus pulposus cells (NPCs). This study explores a novel therapeutic strategy using cell-free fat extract (CEFFE), rich in cytokines, to mitigate IVDD by inhibiting oxidative stress-induced ferroptosis. Methods: In vitro, NPC degeneration was induced by TNF-α/TBHP. The effects of CEFFE on matrix metabolism were evaluated using Western blotting, RT-qPCR, and high-density culture, with regenerative effects measured via CCK-8 assays. Ferroptosis was assessed by Western blotting, immunofluorescence, and electron microscopy. In vivo, rats with caudal IVDD were treated with CEFFE for 4 weeks, and therapeutic efficacy was evaluated through imaging and histological analysis. Results: In vitro, CEFFE reduced TNF-α-induced inflammation and promoted matrix synthesis by inhibiting MAPK and NF-κB pathways. It also activated NRF2 to prevent TBHP-induced ferroptosis. In rats, CEFFE facilitated nucleus pulposus repair and significantly slowed disc degeneration. Conclusions: CEFFE is a promising strategy to delay IVDD progression by inhibiting ferroptosis, offering potential therapeutic benefits for disc degeneration.