Human diabetic mesenchymal stem cells from peripheral arterial disease patients promote angiogenesis through unique secretome signatures.

BACKGROUND: Diabetic patients are at increased risk of complications from severe peripheral arterial disease. Mesenchymal stem cells (MSC) may be useful in limiting these complications. Our objective is to test the angiogenic potential of diabetic versus healthy MSCs.

METHODS: MSCs' angiogenic potential was tested by endothelial cell (EC) proliferation, migration, and 3-dimensional sprouting. Diabetic conditions were simulated with 5.5, 20, or 40 mM glucose. MSC secretome was quantified by enzyme-linked immunosorbent assay.

RESULTS: Human aortic ECs were most sensitive to glucose conditions and were used for all MSC experiments. Diabetic MSCs had greater 3-dimensional invasion than healthy MSCs (P<.05), but EC sprouting was decreased in high glucose conditions in both diabetic and healthy MSCs. Secretome analysis demonstrated that 20mM glucose stimulated epidermal growth factor (EGF) expression in diabetic and healthy MSCs, but that diabetic MSCs had a unique secretome with increased levels of chemokine (C-X-C motif) ligand 1 (CXCL-1), interleukin six (IL-6), and monocyte chemoattractant protein 1 (MCP-1) (P<.05).

CONCLUSION: Despite having similar in vitro angiogenic activity, diabetic MSCs secrete a unique and inflammatory angiogenic signature that may influence MSC survival and function after transplantation in cell therapy applications. Strategies that normalize secretome in diabetic patients may improve the utility of autologous MSCs in this population of patients.