Delayed wound healing and dysregulation of IL6/STAT3 signalling in MSCs derived from pre-diabetic obese mice

• Impaired wound healing in diabetes is a significant health problem.
• Mesenchymal stem cells ability to promote healing is altered in metabolic disorders.
• Primary MSCs derived from pre-diabetic obese animals have refractory mobility.
• Novel evidence of IL6/STAT3 signalling dysregulation, caused by IL6 deficiency.
• Preventative strategies should focus on cellular changes induced by micro-environment.

Metabolic dysfunction that occurs in obesity and Type 2 diabetes results in a low-level inflammatory state which impacts on mesenchymal stem cells (MSCs) capacity to promote wound healing. The ability of either recombinant Interleukin-6 (rIL6) or pioglitazone to modulate MSC migration, essential for wound healing, by targeting the inflammation-modulated IL6/STAT3 signalling pathway was therefore investigated in bone marrow-derived MSCs from control (C57BL/6J) and pre-diabetic obese mice (B6. Cg-Lepob/J). The population doubling time, in vitro wound closure and mRNA expression profile of 84 genes involved in the IL6/STAT3 signalling pathway were assessed. IL6/STAT3 signalling dysregulation, caused by IL6 deficiency, resulted in skewing of the immune modulatory properties of MSCs to favour a pro-inflammatory profile. This could be nullified by addition of either rIL6 or conventional diabetes treatment. Therapies to improve diabetic wound healing should therefore focus on the cellular changes induced by the pathological inflammatory micro-environment.