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Sci Rep. 2019 Feb 19;9(1):2309. doi: 10.1038/s41598-019-38921-z.

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

Author information

1
Cardiovascular Science, The Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
2
Diabetes Research Group, University of Manchester, Manchester, UK.
3
Universiti Kuala Lumpur, Kuala Lumpur, Malaysia.
4
School of Pharmacy, University of Birmingham, Edgbaston, UK.
5
Manchester Academic Health Science Centre, Manchester, UK.
6
Department of Vascular and Endovascular Surgery, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK.
7
Cardiovascular Science, The Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK. f.wilkinson@mmu.ac.uk.

Abstract

Endothelial colony forming progenitor cell (ECFC) function is compromised in diabetes, leading to poor vascular endothelial repair, which contributes to impaired diabetic foot ulcer healing. We have generated novel glycomimetic drugs with protective effects against endothelial dysfunction. We investigated the effect of glycomimetic C3 on the functional capacity of diabetic ECFCs. ECFCs were isolated from healthy controls and patients with diabetes with neuroischaemic (NI) or neuropathic (NP) foot ulcers. Functionally, diabetic ECFCs demonstrated delayed colony formation (p < 0.02), differential proliferative capacity (p < 0.001) and reduced NO bioavailability (NI ECFCs; p < 0.05). Chemokinetic migration and angiogenesis were also reduced in diabetic ECFCs (p < 0.01 and p < 0.001), and defects in wound closure and tube formation were apparent in NP ECFCs (p < 0.01). Differential patterns in mitochondrial activity were pronounced, with raised activity in NI and depressed activity in NP cells (p < 0.05). The application of glycomimetic improved scratch wound closure in vitro in patient ECFCs (p < 0.01), most significantly in NI cells (p < 0.001), where tube formation (p < 0.05) was also improved. We demonstrate restoration of the deficits in NI cells but not NP cells, using a novel glycomimetic agent, which may be advantageous for therapeutic cell transplantation or as a localised treatment for NI but not NP patients.

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