Compromised Antibacterial Function of Multipotent Stromal Cells in Diabetes

Area of Science:

• Immunology
• Cell Biology
• Endocrinology

Background:

• Multipotent stromal cells (MSCs) are crucial for immune regulation.
• Diabetes mellitus is associated with impaired immune cell function.
• The impact of diabetes on MSC antibacterial properties remains unclear.

Purpose of the Study:

• To investigate the antibacterial function of MSCs from diabetic donors.
• To compare the antibacterial activity and immune regulatory capacity of diabetic MSCs versus control MSCs.
• To identify molecular mechanisms underlying potential MSC dysfunction in diabetes.

Main Methods:

• Isolation and culture of MSCs from diabetic and non-diabetic donors.
• Assessment of MSC supernatant's effect on Escherichia coli growth.
• Co-culture of MSCs with human macrophages followed by bacterial phagocytosis assays.
• Gene expression analysis of antibacterial peptides (LL-37) and indoleamine 2,3-dioxygenase (IDO).
• Cytokine profiling using a 42-cytokine antibody array.

Main Results:

• Supernatant from diabetic MSCs (MSCs-dia) promoted E. coli growth compared to control MSCs (MSCs-c).
• Macrophages co-cultured with MSCs-dia exhibited reduced phagocytosis of E. coli.
• MSCs-dia showed decreased expression of LL-37 and IDO compared to MSCs-c.
• LPS stimulation revealed distinct cytokine profiles for MSCs-dia, notably altered MCP-1 and IL-6 production.

Conclusions:

• Diabetic MSCs possess compromised antibacterial capabilities and impaired regulation of macrophage phagocytosis.
• Reduced expression of key antibacterial molecules (IDO, LL-37) and altered cytokine profiles contribute to MSC dysfunction in diabetes.
• Findings highlight the need to account for MSC functional deficits in cell-based therapies for diabetic patients, particularly concerning infection risk.