Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Abstract

Diabetic foot ulceration is a chronic complication in diabetes where tissue damage occurs due to neuropathy, ischemia and/or infection1 and given its resistance to treatment, provides the impetus for development of novel healing modalities. Chronic wounds are characterized by a persistent inflammatory phase, often complicated with infection, and a failure of defence cell response to damaging micro-environmental stimuli and often results in amputation2. One of the notable characteristics of diabetic macroangiopathy (DM), is the prevalence of coexistent coronary disease3,4 and vascular calcification5, which results in chronic limb ischemia (or CLI) caused by a compromised repair process and ultimately increases risk of mortality4. Despite the compromised angiogenic process in diabetes, associated with endothelial dysfunction and microvascular complications6, stem or progenitor cell therapy shows promise for repair of ischemic tissue through neovascularisation7. A meta-analysis of studies using stem cell therapy, suggests enhanced diabetic foot ulcer healing and outcomes, reducing pain, lowering amputation rate and improving prognosis compared with standard treatment8,9. Although there reports demonstrate the impact of endothelial progenitor cells (EPC) in vascular regeneration10–12, no studies have evaluated functional distinction between cells isolated from neuroischemic (NI) versus neuropathic (NP) patients. Both NI and NP patients exhibit neuropathy, which may be caused by a breakdown in homeostatic metabolic and vascular factors, contributing to impaired wound healing through reduced oxygen delivery, nutrients and angiogenic growth factors13. The first part of this study aimed to determine whether distinctive differences could be identified between ECFCs isolated from patients with NI vs NP wounds, and establish whether this could contribute to impaired would healing.