Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration

Although mesenchymal stromal cell (MSC) implantation shows promise for repairing intervertebral disc (IVD) degeneration (IVDD), their limited retention within degenerative IVDs compromises therapeutic efficacy. The oxidative stress in the microenvironment of degenerated IVDs induces a surge in reactive oxygen species production within MSCs, disrupting the balance between oxidation and antioxidation, and ultimately inducing ferroptosis. Recent evidence has suggested that targeting ferroptosis in MSCs could enhance MSC retention, extend the survival of transplanted MSCs, and markedly delay the pathological progression of IVDD. By targeting ferroptosis, a novel approach emerges to boost the efficacy of MSC transplantation therapy for IVDD. In this review, current research on targeting ferroptosis in MSCs is discussed from various perspectives, including the targeting of specific genes and pathways, drug preconditioning, and hydrogel encapsulation. A detailed discussion on the effects of targeting ferroptosis in MSCs on the transplantation repair of degenerated IVDs is provided. Insights that could guide improvements in stem cell transplantation therapies are also offered. Significantly, this review presents specific ideas for our future foundational research. These insights outline promising avenues for future clinical translation and will contribute to developing and optimizing treatment strategies for MSC transplantation therapy, maximizing benefits for patients with lumbar IVDD.