Advancing Intervertebral Disc Biology via Omics: Implications for Nucleus Pulposus Progenitor Cell-Based Regeneration.

Background: Intervertebral disc (IVD) degeneration (IDD) contributes to global disability and involves incompletely understood molecular processes. Recent advances in omics technologies help to unravel the complex biology of IDD and develop novel therapies. Methods: This narrative review explores how omics approaches-particularly RNA sequencing-have advanced our understanding of IVD biology and how these findings contribute to leveraging the intrinsic regenerative potential of the IVD, with a specific focus on nucleus pulposus progenitor cells (NPPCs). Relevant literature addressing transcriptomic, genomic, proteomic, metabolomic, and epigenetic data, as well as emerging mult-iomics approaches, was summarized. Results: Single-omics studies have provided insight into cellular heterogeneity, gene expression changes, genetic susceptibility loci, proteomic changes, metabolic alterations, and epigenetic regulation. Further, they have highlighted key pathways associated with extracellular matrix remodeling, inflammation, and progenitor cell depletion in IDD. Inconsistencies between Conclusions: Although NPPCs hold promise for IVD regeneration, translational challenges such as cell survival and efficacy persist. Omics-informed insights into the IVD microenvironment may support the development of combinatorial strategies, including co-delivery of modulators to enhance NPPC survival and the effectiveness of therapies.