“…A decrease in the AF cell density, as frequently observed in degenerated IVDs, alters the balance of anabolism:catabolism ratio in the extracellular matrix (ECM), changing the AF mechanical, biological, and structural properties [ 69 , 70 , 71 ]. Therefore, regenerative strategies aim to repopulate a degenerated IVD with healthy cells (cell therapy) or stimulating the existing cells to regulate the ECM reaching an enhanced composition, quantity, and structure (biomolecule and gene therapy) [ 81 , 82 , 83 , 84 , 85 ]. ECM remodeling is crucial to control the action of biochemical mediators such as cytokines (interleukins), growth factors, and enzymes (metalloproteinases and heparanase) to ultimately stop or reverse the IVD degeneration process [ 86 , 87 , 88 , 89 ].…”