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An Anti TNF-A Receptor Antagonist does not Augment the Effect of Autologous Mesenchymal Stem Cell Therapy in Experimental Intervertebral Disc Degeneration in Göttingen Minipigs

Bendtsen M, Zou X, Jørgensen HS and Bünger CE

Study design: Intervertebral disc degeneration (IDD) was induced surgically in 16 skeletally mature Göttingen minipigs. Autologous stem cells were transplanted 12 weeks post-operatively. Half f the animals were randomized to Humira® treatment 6 prior to 6 weeks after stem cell transplantation. Total observation was 30 weeks. Objective: To evaluate whether anti TNF-α antibody administered systemically for a short period augmented the regenerative effect of autologous stem cell therapy. Summary of Background data: Anti TNF-α treatment have been tested with regard to resorption of disc herniation and sciatica without significant effect. It is a second line treatment in inflammatory bowel disease and rheumatoid arthritis. It is thought as a pain modulator and inhibits chondrocytic differentiation. Mesenchymal stem cell therapy has some proven efficacy in regeneration of the degenerative intervertebral disc. Methods: IDD was induced by full thickness scalpel incisions in 3 levels in 16 skeletally mature Göttingen minipigs. Stem cells were harvested and purified from bone marrow and transplanted after 12 weeks. Half of the animals were randomized to short term treatment with anti TNF-α antibody (Humira®, Abbott Laboratories) for 6 weeks before to 6 weeks after stem cell treatment. Total observation was 30 weeks. MRI was performed before stem cell transplantation and before sacrifice. Quantitative real time RT-PCR and histology was performed after sacrifice. Results: Autologous stem cell transplantation was able to stop and partially reverse the degenerative process with regard to MRI index (p=0.0031), disc height (p=0.021 and 0.04) and ADC value (p=0.023). Quantitative real time RT-PCR found no difference in apoptosis markers between any of the groups. Histology showed partial degeneration in stem cell treated discs. There was no difference in any parameter between groups treated with Humira® or not. Conclusion: Autologous stem cell therapy is able to stop and partially reverse the degenerative process and survive in vivo for at least 18 weeks. Anti TNF-α treatment does not augment the effect and does not slow down the degenerative process in a minipig model of IDD.