The microenvironment resulting from the co-culture of human amniotic fluid-derived mesenchymal stem cells with peripheral blood mononuclear cells differs between type 1 diabetes mellitus patients and healthy individuals

Abstract IFNγ is one of the main factors involved in type 1 diabetes (T1D) pathogenesis and has also been used to license mesenchymal stem cells (MSCs) for displaying immunosuppressive properties in a process termed preconditioning/priming. Our study aimed to investigate the interaction of amniotic fluid-derived MSCs (AF-MSCs) in two preconditioned (IFNγ⁺) and non-preconditioned (IFNγ⁻) conditions, with peripheral blood mononuclear cells (PBMCs) from the sources of healthy control (HC) and T1D. Accordingly, the interactions were assessed through anti-inflammatory genes, chemokines and their receptors, plus the induction of T regulatory (Treg) cells. Our results demonstrated that MSC/IFNγ⁺ and MSC/IFNγ⁻ treatments respond conversely to HC and T1D PBMCs regarding the expression of anti-inflammatory genes ( IDO1 , IDO2 , ICAM-1 ), chemokine ligands ( CCL3 , CXCL9, CXCL10 ) and receptors involved in immune cell trafficking ( CXCR3 , CXCR6 , TLR4 ). Our findings also confirmed the same opposite effects of HC and T1D PBMCs when interacting with IFNγ⁺ and IFNγ⁻ MSCs regarding the expression of target genes, including CXCR3 and its ligands ( CXCL9 and CXCL10 ), CXCR6 , CCR5 and its ligands ( CCL3 and CCL4 ). These differences were also reflected in the proportion of Treg cells in HC and T1D samples, depending on whether it was assessed through paracrine or cell contact approaches. Our research indicates that the interaction between IFNγ⁺ and IFNγ⁻ MSCs and T1D PBMCs creates distinct microenvironments compared to those in HC PBMCs. This implies that the intravenous administration of MSCs into T1D patients may result in different outcomes than in healthy individuals that can be manipulated by the preconditioning of MSCs.