Mesenchymal Stem Cells (MSCs) Influence the Differentiation of Regulatory T cells and Th17 Cells for the Treatment of Systemic Lupus Erythematosus (SLE)

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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