Recent Advances in Cell and Gene Therapy for Intervertebral Disc Degeneration: From Molecular Targets to Translational Strategies

Low back pain is one of the leading causes of disability worldwide, imposing substantial socioeconomic burdens on healthcare systems and society. Intervertebral disc degeneration (IVDD) is recognized as one of the most important pathological contributors. The intervertebral disc — composed of nucleus pulposus, annulus fibrosus, and cartilage endplates — gradually loses structural and functional integrity under aging, mechanical overload, genetic susceptibility, metabolic disturbances, and inflammatory microenvironmental changes.Over the past decade, substantial progress has been made in identifying the molecular and cellular drivers of IVDD that are amenable to genetic and cellular intervention. Mitochondrial dysfunction, oxidative stress, extracellular matrix imbalance, cellular senescence, and regulated cell death pathways (apoptosis, pyroptosis, ferroptosis, necroptosis) have revealed specific molecular targets for therapeutic correction. In parallel, non-coding RNAs, epigenetic modifiers, and stem cell–derived secretomes — including exosomes and other extracellular vesicles — have emerged as powerful entry points for gene- and cell-based therapies aimed at restoring disc homeostasis.Cell therapy strategies using mesenchymal stromal cells, nucleus pulposus progenitors, induced pluripotent stem cell derivatives, and genetically engineered progenitors are being actively explored to replenish disc cell populations and modulate the degenerative microenvironment through paracrine and immunomodulatory functions. Gene therapy approaches — including viral and non-viral vector delivery, CRISPR/Cas-based gene editing, RNAi, mRNA, and antisense oligonucleotide therapeutics — are opening new avenues to correct molecular causes of degeneration and to reprogram disc cell fate. Cell-free strategies based on extracellular vesicles and engineered secretomes further expand the translational toolbox.This Research Topic aims to gather cutting-edge basic and translational studies that advance the development and application of innovative genetic and cellular therapies for intervertebral disc degeneration, bridging molecular mechanism discovery with therapeutic implementation.We welcome Original Research, Reviews, Mini Reviews, Methods, and Perspectives addressing, but not limited to:o Mechanisms of disc cell senescence, regulated cell death, and matrix homeostasis that identify molecular targets for cell or gene therapyo Stem and progenitor cell biology of the intervertebral disc, including advanced cell culture systems and disc-derived organoidso Cell therapies for disc repair, including mesenchymal stromal cells, nucleus pulposus progenitors, and iPSC-derived cellso Paracrine and immunomodulatory functions of therapeutic cells, including exosomes and extracellular vesicles for cell-free disc regenerationo Ex vivo genetic modification of progenitor cells for disc regenerationo Gene-, peptide-, and RNA-based therapeutics (mRNA, siRNA, miRNA, ASO, lncRNA) targeting IVDDo Gene editing approaches (CRISPR/Cas and related technologies) for correction of degeneration-associated molecular targetso Viral and non-viral vector development for targeted gene delivery to disc cellso Epigenetic regulation as a therapeutic target in disc degenerationThe Research Topic contributes to Sustainable Development Goals (SDGs) 3 (Good Health and Well-being) and 9 (Industry, Innovation, and Infrastructure).Out of scope: In line with the Cell and Gene Therapy section policy, this Research Topic does not consider bibliometrics articles, clinical studies, or manuscripts focused solely on bioinformatic analyses of existing databases without significant experimental validation. Submissions centered on surgical outcomes, survival analysis, risk prediction, or purely biomaterial/scaffold/biomechanical studies without a genetic or cellular therapeutic component are also outside the scope. Topic editors: Pengzhi Shi, Bo Han, Fabrizio Russo Source: https://www.frontiersin.org/research-topics/85811/recent-advances-in-cell-and-gene-therapy-for-intervertebral-disc-degeneration-from-molecular-targets-to-translational-strategies