Abstract 16943: Abnormal Immunomodulatory Function of Mesenchymal Stem Cells From Elderly Patients With Coronary Artery Disease: A Novel Pro-Atherogenic Mechanism?
BACKGROUND: Advancing age and its associated chronic low-grade inflammatory state known as “inflammaging” are risk factors for the development and progression of atherosclerosis and cardiovascular disease. Mesenchymal stem cells (MSC) are powerful modulators of the innate and adaptive immune systems, and are currently evaluated as potential therapies for atherosclerosis and other chronic inflammatory disorders. It is unknown whether advancing age affects the immunomodulatory functions of MSC, and whether MSC senescence could thereby promote atherosclerosis.
METHODS: MSC were derived from human adipose tissue obtained from patients undergoing coronary artery bypass graft surgery (CABG). We characterized the MSC phenotype according to standard criteria and assessed their capacity to suppress activated human peripheral blood T cells in allogeneic MSC: T cell co-cultures. The mechanisms involved in the interaction, whether via direct cell contact and/or via soluble mediators, were evaluated in trans-well experiments. The MSC secretome was profiled with cytokine arrays, and cytokine levels were determined by ELISA.
RESULTS: MSC from CABG patients exhibit an age-dependent decline in their capacity to suppress the proliferation of activated T cells (n=27, p=0.04). Soluble factors and to a lesser extent cell-cell contact mediate the MSC: T cell interactions. Among the soluble factors, there was an age-dependent increase in the MSC secretion of IL-6, a pro-inflammatory senescence associated cytokine (n=10, p=0.01). IL-6 levels inversely correlated with the MSC immunomodulatory capacity, and the decreased MSC function was improved by adding anti-IL-6 mAb to cultures (n=4, p=0.02).
CONCLUSION: There is a decline in the immunomodulatory capacity of MSC from elderly atherosclerotic individuals. Their MSC have an increased production of IL-6 that could promote the pro-inflammatory state associated with aging and atherosclerosis. These findings will help optimize the selection of MSC donors for cell-based therapies.
- © 2013 by American Heart Association, Inc.