The Inflammatory Milieu of the Degenerate Disc: Is Mesenchymal Stem Cell-based Therapy for Intervertebral Disc Repair a Feasible Approach?

Intervertebral disc degeneration is directly linked to chronic low back pain, a condition that affects multitudes of people world-wide and presents tremendous direct and indirect health costs. Water-loss, inflammation and disruption of the extracellular matrix ultimately result in loss of tissue function and associated pain. Cytokines present in degenerate tissue can upregulate protease activity and directly causes pain. Non-invasive therapies provide limited efficacy for pain management, and surgical intervention is therefore often required to treat chronic low back pain. Disc removal can offer immediate pain-relief, however degeneration of adjacent segments can occur and pain can return. To circumvent the caveats of recurring pain and invasive surgeries, stem cell therapy is currently being investigated as a promising means to repair degenerating discs. However, while initial studies have shown promise, few studies have addressed whether stem cell therapies can modulate the inflammatory microenvironment or whether cytokines can affect the ability of the implanted cells to repair damaged tissue. This review focuses briefly on mechanisms of disc degeneration, with more attention given to the role of inflammatory milieu in this process. Cytokine upregulation in disc degeneration, the potential role of toll-like receptor signaling, and effects of these inflammatory factors on stem cells will be discussed. We find that while stem cell differentiation can be negatively influenced by inflammatory cytokines, stem cells can potentially have antiinflammatory effects. We conclude that further investigation of stem cell interactions with the inflammatory microenvironment is required, and that priming of stem cells under various conditions may be necessary for optimal therapeutic value for intervertebral disc repair and pain reduction.