The role of nucleus pulposus progenitor cells in intervertebral disc degeneration and regeneration

Intervertebral disc degeneration (IDD) is a significant public health issue, commonly associated with symptoms such as low back pain (LBP), and poses a substantial burden on both society and affected families. The pathogenesis of IDD primarily involves the depletion and impaired function of nucleus pulposus (NP) cells, as well as alterations in the extracellular matrix (ECM) composition. Current clinical management strategies, including conservative and surgical treatments, aim primarily to alleviate symptoms rather than reverse the pathological process or promote structural regeneration of the intervertebral disc (IVD). In recent years, studies have identified the presence of nucleus pulposus progenitor cells (NPPCs) within the NP region and characterized specific surface markers associated with these cells. Due to their ability to adapt to the harsh, nutrient-poor IVD microenvironr potential to effectively differentiate into NP-like cells, NPPCs have emerged as a promising candidate for cell-based regenerative therapies aimed at IVD repair. A deeper understanding of the biological properties and regulatory mechanisms of NPPCs is crucial for advancing their therapeutic application. This review summarizes current knowledge on NPPCs, including their characteristics, pathological alterations and associated signaling pathways during disc degeneration, and recent advances in NPPC-based therapies for IDD. Finally, the ongoing challenges for the clinical translation of NPPC-based therapies are discussed, along with potential directions for future research.