Immunomodulation of mesenchymal stem cells in discogenic pain.

BACKGROUND CONTEXT: Back pain is a highly prevalent health problem in the world today and has a great economic impact on health-care budgets. Intervertebral disc (IVD) degeneration has been identified as a main cause of back pain. Inflammatory cytokines produced by macrophages or disc cells in an inflammatory environment play an important role in painful progressive degeneration of IVD. Mesenchymal stem cells (MSCs) have shown to have immunosuppressive and anti-inflammatory properties. Mesenchymal stem cells express a variety of chemokines and cytokines receptors having tropism to inflammation sites. PURPOSE: This study aimed to develop an in vitro controlled and standardized model of inflammation and degeneration of IVD with rat cells and to evaluate the protective and immunomodulatory effect of conditioned medium (CM) from the culture of MSCs to improve the conditions presented in herniated disc and discogenic pain processes. STUDY DESIGN: This is an experimental study. METHODS: In this study, an in vitro model of inflammation and degeneration of IVD has been developed, as well as the effectiveness of CM from the culture of MSCs. RESULTS: Conditioned medium from MSCs downregulated the expression of various proinflammatory cytokines produced in the pathogenesis of discogenic pain such as interleukin (IL)-1ß, IL-6, IL-17, and tumor necrosis factor (TNF). CONCLUSION: Mesenchymal stem cells represent a promising alternative strategy in the treatment of IVD degeneration inasmuch as there is currently no treatment which leads to a complete remission of long-term pain in the absence of drugs.

The role of different hyaluronic acids in the articular cartilage of rabbit.

PURPOSE: To elucidate if the differences found in the physico-chemical and rheological behaviour of Hyaluronic Acids result in different in vivo activity. For this purpose two Hyaluronic Acids (HA), HA-1 and HA-2, with similar molecular weight but different percentage of concentration variation, were compared through an osteoarthritis model. METHODS AND MATERIALS: Osteoarthritis was induced in white New Zealand rabbits by anterior cruciate ligament section. After the induction period, the animals were allocated to receive HA-1 or HA-2 intra-articularly in one knee whereas the contralateral knee was used as Operated Control. An additional group of non-operated animals was used as Healthy Controls. Samples of cartilage were taken for different measures: apoptosis, nitric oxide (nitrites) and hyaluronic acid in synovial fluid. RESULTS: The administration of HA-1 had a significant inhibitor effect on apoptosis of the chondrocytes compared to operated untreated animals (p = 0.0089), whereas this difference was not observed in the HA-2 knees. Levels of nitrites determined by HPLC in the HA-1 knees were similar to those in the Healthy group (p = 0.6551) whereas they were significantly higher in Operated Control and HA-2 groups (p = 0.0001). The comparison between HA-1 and HA-2 also revealed significantly lower levels of nitrites in the HA-1 knees (p = 0.0001). Values of hyaluronic acid in synovial fluid did not show statistical differences between the different study groups. CONCLUSIONS: HA-1 and HA-2 showed different physico-chemical characteristics and these differences have resulted in different in vivo behaviour. As a consequence, not all the HA with similar molecular weight can be considered as equivalent.