The effect of poly I:C or LPS priming on the therapeutic efficacy of mesenchymal stem cells in an adjuvant-induced arthritis rat model

Background The immunomodulatory properties of mesenchymal stem cells (MSCs) have made them a prospective treatment option for inflammatory and autoimmune disorders. Recent studies have found an association between the immunomodulatory function of MSCs and Toll-like receptors (TLRs). Here, we investigated the effect of priming with lipopolysaccharide (LPS) as TLR4 ligand or polyinosinic:polycytidylic acid (poly I:C) as TLR3 ligand on the immunomodulatory function of adipose-derived MSCs (ADMSCs) in vitro and for the first time in an adjuvant-induced arthritis model (AIA). Methods ADMSCs were treated with LPS or poly I:C for 1 h. Splenocyte proliferation in the presence of primed ADMSCs was assessed in vitro using an MTT assay. Next, we investigated the therapeutic effect of primed ADMSCs in vivo. Male Wistar rats were infused with complete Freund's adjuvant (CFA) to develop arthritis and then intraperitoneally treated with not-primed, poly I:C- or LPS-primed ADMSCs. Clinical signs, histopathological alteration, and serum and spleen cytokine levels were analyzed. Results Poly I:C-primed ADMSCs significantly reduced splenocytes proliferation, while ADMSCs primed with LPS increased splenocytes proliferation. Furthermore, poly I:C-primed ADMSCs significantly alleviated the clinical and histopathological severity and the secretion of inflammatory cytokines associated with Th17/Th1 such as IL-17 and IFN-gamma. Poly I:C-primed ADMSCs also increased cytokines IL-10 and TGF-beta. TNF-alpha and IL-6 Levels were also markedly diminished in the serum of AIA animals treated with poly I:C-primed ADMSCs. In contrast, priming ADMSCs with LPS significantly reduced the therapeutic effect of ADMSCs in AIA animals. Conclusion As a result of these findings, poly I:C priming may be a new technique for improving the therapeutic effects of MSCs in arthritic disorders.

Automated summary

In this study, the effect of priming adipose-derived mesenchymal stem cells (ADMSCs) with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) on their immunomodulatory function was investigated. The results showed that priming with poly I:C significantly reduced splenocyte proliferation mediated by ADMSCs and alleviated the clinical and histopathological severity of arthritis. Furthermore, poly I:C-primed ADMSCs also decreased the secretion of inflammatory cytokines and increased the levels of anti-inflammatory cytokines. In contrast, priming with LPS reduced the therapeutic effect of ADMSCs in the arthritis model.