Investigation into a novel endothelial progenitor cell-based treatment strategy to promote diabetic wound healing.

The specific mechanisms leading to poor wound healing in people with diabetes are not well understood. In this research project we aim to identify the possible mechanisms to improve wound healing in people with diabetes, and use EPCs to promote therapeutic angiogenesis via a novel cell-based treatment patch.

Preliminary work
We have an ongoing collaboration with physicians and podiatrists at the Manchester Diabetic Foot Clinic in Rusholme to recruit patients and collect blood samples from diabetic foot ulcer patients and isolate EPCs from these samples using an isolation and culture technique that is now well-established within our laboratory. Over 20 samples have been collected to date and we have further stratified the patient groups into those with neuroischaemia and those with neuropathy in order to investigate the different disease mechanism between these two groups. We have successfully cultured EPCs from both sets of patients and current work is ongoing to assess the function of the diabetic EPCs in these distinct patient groups compared to those isolated from healthy controls.

Project objectives
This project will extend our current studies with the following objectives:
1) Determine the functional characteristics of EPCs from the diabetic patients with two distinctive ulcer types, and compare them to healthy control EPCs. This will include their proliferation, migratory and adhesion capacity and response to chemotactic agents. In addition, we will perform secretome analysis, where we will investigate the effect of diabetic EPC conditioned media on healthy cells and identify the aberrant molecular signalling pathways responsible for the defective function of diabetic EPCs.
2) Investigate novel biomarkers for diabetic wound healing capacity. In addition to colleting blood for EPC isolation, we have also collected and stored plasma samples from diabetics and healthy controls. This will be used for downstream proteomic screening to probe the global protein expression profile of diabetic patients with poor wound healing capacity and identify novel therapeutic targets.
3) Enhance the therapeutic angiogenic potential of EPCs. Studies have shown that certain molecules, for example stem cell-derived factor 1 (SDF-1), have the ability to promote the migratory capacity of EPCs. A further project aim would be to enhance the performance of patient-derived EPCs by transfection with SDF-1 and assess this in both in vitro and in vivo.