Compromised Antibacterial Function of Multipotent Stromal Cells in Diabetes

In diabetes, multipotent stromal cells (MSCs) are functionally deficient. It is unknown, however, whether their antibacterial function is compromised. In this study, MSCs were isolated from the bone marrow samples provided by nine diabetic and six nondiabetic donors and treated with or without Escherichia coli lipopolysaccharides (LPS). The supernatant of diabetic MSCs (MSCs-dia) and nondiabetic control MSCs (MSCs-c) was added into the cultures of E. coli for evaluation of the effect of MSCs-dia and MSCs-c on bacterial growth. The number of E. coli colonies increased when they were cultured with the supernatant of MSCs-dia, with or without LPS stimulation, compared with the E. coli cultured with the supernatant of MSCs-c. Human macrophages were co-cultured with either MSCs-dia or MSCs-c, for 24 h, and then cultured with heat-inactivated E. coli. Bacterial phagocytosis was reduced after macrophages were co-cultured with MSCs-dia. Gene expression of antibacterial peptide LL-37 and indoleamine 2,3-dioxygenase (IDO) by MSCs-dia was reduced compared with MSCs-c. The supernatant of MSCs-dia and MSCs-c was applied to a 42-cytokine antibody array. While the cytokine profiles of MSCs-dia and MSCs-c were largely similar, the productions of MCP-1 and interleukin-6 distinguished MSCs-dia from MSCs-c in response to LPS treatment. In conclusion, MSCs-dia were less inhibitive of the growth of bacteria and compromised in regulation of macrophages for bacterial phagocytosis. The reduced expression of IDO and LL-37 and an altered cytokine profile in MSCs-dia should be taken into consideration in developing cell therapies for diabetic infection.