SAT0169 Impaired migration and proliferation of bone marrow-derived mesenchymal stem cells from patients with systemic lupus erythematosus were mediated by IKK-β
Authors: L. Geng, J. Zhang, X. Li, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvements and a wide array of clinical manifestations. There is increasing evidence that dysregulation of stem cells is involved in the pathogenesis of SLE. Bone marrow-derived mesenchymal stem cells (BMMSCs), characterized by their self-renewal and pluripotent differentiation capability, are non-hematopoietic cells located in bone marrow microenvironment. Previous studies found that BMMSCs by intravenous infusion could migrate to the injury site to repair the damage site. In addition, allogenic MSC transplantation (MSCT) appeared to be a feasible and safe therapy strategy in refractory and severe SLE patients and lupus mice. Moreover, our previous data showed that SLE BMMSCs growing more slowly with early signs of senescence, indicating that SLE BMMSCs might have function defects in migration and proliferation. Studies found that tumor necrosis factor-α (TNF-α) might play an important role in migration and proliferation of BMMSCs by activating the NF-κB signaling pathway, during which IkB-kinase complex (IKK-β) acts as a key role. <h3>Objectives</h3> The aim of this study was to observe whether SLE BMMSCs exhibited abnormalities of migration and proliferation, and to investigate the effect of IKK-β on migration and proliferation of SLE BMMSCs which might contribute to the disease pathogenesis. <h3>Methods</h3> BMMSCs were isolated, cultured and expanded from iliac crest bone marrow of six healthy controls and six SLE patients. Migration of BMSCs was observed by wound healing and trans-well migration assays. Proliferation of BMSCs was quantified by cell counting Kit-8 assay. TNF-α level in the serum from healthy controls and SLE patients was detected by ELISA. Real-time PCR technique and Western blot analysis were used to determine the IKK-β expression mRNA and protein levels and phosphorylation-IKK-β (p-IKKβ) expressions. Finally, the IKK-β inhibitor and TNF-α were added individually to detect their effect on migration and proliferation of BMMSCs from healthy controls and SLE patients. <h3>Results</h3> The migration rate and proliferation of SLE BMMSCs (5.23±3.85‰ and 0.21±0.49, respectively) were remarkably decreased compared with that of healthy controls (7.014±2.92‰ and 1.0±0.35, respectively; <i>p</i>&lt;0.05). No difference was observed in IKK-β mRNA level between SLE patients and healthy controls, while IKK-β protein expression of SLE BMMSCs was increased significantly compared with that of healthy controls (<i>p</i>&lt;0.05). Compared with healthy controls (115.23±31.55pg/ml), the levels of TNF-α were significantly elevated in SLE patients (242.88±49.95pg/ml, <i>p</i>&lt;0.001). Inhibitor of IKK-β caused a significant increase in migration and proliferation of BMMSCs from healthy controls and SLE patients (<i>p</i>&lt;0.05), while TNF-α led to an opposite effect (<i>p</i>&lt;0.05). <h3>Conclusions</h3> Migration and proliferation of BMMSCs were significantly decreased in SLE patients, which might be associated with the up-regulation of IKK-β stimulated by TNF-α. <h3>Disclosure of Interest</h3> None Declared