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

Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101234999 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2299-5684 (Electronic) Linking ISSN: 17341140 NLM ISO Abbreviation: Pharmacol Rep Subsets: MEDLINE

Publication: 2020- : Cham, Switzerland : Springer International Publishing
Original Publication: Kraków, Poland : Institute of Pharmacology, Polish Academy of Sciences, c2005-

Arthritis, Experimental*/chemically induced ; Arthritis, Experimental*/therapy ; Mesenchymal Stem Cell Transplantation*/methods ; Mesenchymal Stem Cells*; Animals ; Cytokines ; Ligands ; Lipopolysaccharides/pharmacology ; Male ; Poly I-C/pharmacology ; Rats ; Rats, Wistar

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-γ. Poly I:C-primed ADMSCs also increased cytokines IL-10 and TGF-β. TNF-α 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.
(© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

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Keywords: Adjuvant-induced arthritis; Immunomodulation; LPS; Mesenchymal stem cells; Poly I:C; Toll-like receptor

0 (Cytokines)
0 (Ligands)
0 (Lipopolysaccharides)
O84C90HH2L (Poly I-C)

Date Created: 20220717 Date Completed: 20220805 Latest Revision: 20220811

20240104

10.1007/s43440-022-00386-9

35842893