Wound healing in diabetes with innate immune molecules and cells

A major medical problem in our ageing population are diabetic foot. These chronic wounds result in extreme discomfort. We will use our knowledge and technical know-how about acute infammation and the involved cytokines, chemokines and proteases to develop a completely new strategy to tackle this problem. Diabetic feet develop in patients, who have insufficient glycemia control, whereas pressure sores are caused by compression of the neurovascular supply to the skin. Vascular insufficiency leads to a chronic status with necrosis (and dry wounds). Granulation tissue (wet wounds) usually yield better healing and are the result of an acute inflammatory status whereby chemokine-attracted neutrophils not only provide the necessary defense against viral and bacterial infections but also provide angiogenic key signals for revitalization and tissue reconstitution by progenitor cells.

We will study a new concept for rejuvenation of dying and necrotic tissue by inducing matrix remodeling and angiogenesis by immune-stimulating molecules and drugs. Our previous insights in acute and chronic inflammation provides the fundamental basis for this concept. Our approach combines (1) profiling and understanding the pathogenesis of pressure ulcers by RNA-sequencing, (2) finding molecules with beneficial effects and (3) defining new treatment options in animal models and, eventually, in a first clinical assessment. Unlike with expensive patient-tailored (personalized) stem cell therapy, pharmacological precision boosting of endogenous mechanisms of immune molecules (cytokines and chemokines) and cells (mainly neutrophils) will be used to reactivate atone dry necrotic wounds into wet neutrophil-rich granulation tissues and to induce healing. In this way we want to boost endogenous anabolism to fortify otherwise frail patients. /