Cell-based therapies for intervertebral disc degeneration: Navigating the path from promise to clinical reality

Low back pain (LBP) remains a leading contributor to global health loss, with its disease burden escalating steadily worldwide. Intervertebral disc degeneration (IDD) serves as the primary pathological basis for specific forms of LBP, driven by a multifactorial cascade involving molecular, biochemical and structural alterations. Conventional conservative treatments merely mitigate symptoms without abrogating or reversing the degenerative process, while surgical interventions-though effective for relieving neural compression-fail to regenerate damaged disc tissue and carry inherent risks such as recurrence. In this context, cell-based therapies have emerged as a major focus of regenerative research for IDD, offering unique potential to facilitate tissue repair and ameliorate pain. Nevertheless, substantial hurdles endure: the mechanisms of action remain incompletely defined, standardized cell products are lacking, and robust evidence supporting long-term safety and efficacy is scarce. This review focuses on cell-based therapies for IDD, systematically examines the global research landscape and recent advances, investigates the proposed mechanisms of action, analyzes the current status of clinical research, and outlines future directions, aiming to inform and guide further exploration in this rapidly evolving field. The Translational Potential of this Article: This work systematically synthesizes current research landscape of cell-based therapies for IDD, elucidates key translational hurdles, and proposes actionable solutions, delivering critical guidance to accelerate the translation of cell-based therapies into clinical practice.