Iain Bryant

Introduction: Systemic Lupus Erythematosus (SLE) is a systemic complex autoimmune disease. Immune complex formation and deposition in various tissue provide a wide framework of symptoms including, but not limited to, vasculitis, nephritis, and arthritis.¹ Additionally, studies have shown that roughly 80% of cases occur in women and incidence among African Americans two to three times greater than Caucasians. ^2,3,4 Current treatment includes corticosteroids, immunosuppressants and monoclonal antibodies, but these treatments come with significant adverse effects and costs.¹ Even with these treatments, roughly 20% of patients remain refractory and thus require a new avenue of treatment.¹ Mesenchymal Stem Cells (MSCs) have been shown to downregulate the autoinflammatory processes of SLE and are readily harvested from Umbilical Cord Blood (UB-C), Adipose Tissue and Bone Marrow. In particular, MSCs have been shown to influence the differentiation of the pro-inflammatory Th17 cells and the anti-inflammatory T regulatory cells.⁶ Th17 cells have shown significant upregulation in those with active SLE and downregulation upon conventional treatment.⁵ Conversely, T regulatory cells have shown the opposite trend in that active SLE patients have significantly depressed populations of T regulatory cells and they are upregulated following conventional treatment.⁵ Methods: The proposed ability of MSCs to influence the differentiation of the T regulatory cells and the Th17 cells lies in the secretion of soluble factors such as TGF-ß and the downregulation of TNF-⍺.⁶ Cell cultures of MSCs and peripheral blood mononuclear cells (PBMCs) obtained from Lupus patients demonstrated that, once treated with anti-TGF-ß antibodies, levels of T regulatory cells decreased back to pre-treatment levels.⁶ Furthermore, cell cultures that included a transwell demonstrated that the differentiation of the T cell populations was cell contact independent.⁶ MSCs also exhibited a dose dependent relationship for treatment.⁶ Finally, it was found that MSCs could also provide an avenue for combination therapy as the efficacy of a combination therapy of MSCs and conventional corticosteroids provided better outcomes than the individual therapies on their own.⁷ Results: MSCs have shown promise as a potential avenue of treatment for SLE refractory to conventional therapy. One of the proposed mechanism of action is through the manipulation of soluble factors TGF-ß and TNF-⍺.

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