Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE₂ pathway

Abstract

Background Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factor-beta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E 2 (PGE 2 ) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE 2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE 2 , which induces macrophage polarization and increases regulatory T-cell numbers.

Stromal cell therapy in cats with feline chronic gingivostomatitis: current perspectives and future direction

“… 34 Specifically, it was determined that secretion of anti-inflammatory cytokine prostaglandin E2 (PGE2) by IFN-γ-pretreated adMSCs induces macrophage and T-cell polarization towards tolerogenic and anti-inflammatory phenotypes. 35 IFN-γ stimulation is especially relevant in FCGS cats, because this pro-inflammatory cytokine is upregulated at the systemic level in these patients. 12 Consequently, adMSC treatment reduces IFN-γ levels in patients with FCGS.…”

Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species

“…In this regard, it is logical to find that pre-conditioning MSCs with IFN-γ results in increased expression of IDO, and of other key immunomodulatory molecules such as prostaglandin (PG)E-2, transforming growth factor (TGF)-β, NO, IL-10, tumor necrosis factor-inducible gene 6 protein (TSG-6) and Programmed deathligand 1 (PD-L1). These molecules can suppress the cytotoxic activity of natural killer (NK) cells, lymphocyte proliferation and cytokine secretion (113)(114)(115)(116), and macrophage polarization (116,117). Additionally, priming MSCs with IFN-γ has been shown to impair a type 3 immune response characterized by cells that produce IL-17 (118).…”

Clinical application of both amniotic membranes and adipose derived mesenchymal stem cells in a cat with a large skin defect

“…On day 20, from the adipose tissue, mesenchymal stem cells were cultivated with the help of the Department of Internal Medicine at Seoul National University. Detailed information related to the mesenchymal stem cells can be found through a previously published article (Park et al 2021). The mesenchymal stem cells were intradermally injected in the wound lesions after being premedicated with dexamethasone (Jeil Dexamethasone injection, Jeil Pharmaceutical Co, Ltd, Yongin, Republic of Korea) 0.2 mg/kg, i.v., and chlorpheniramine (Chlorpheniramine Maleate injection; Huons, Co, Ltd, Seoul, Republic of Korea) 0.5 mg/kg, i.v., four times every other day (Figure 3A).…”