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

Research output: Contribution to journalArticle

Authors

  • Alexander W W Langford-Smith
  • Ahmad Hasan
  • Ria Weston
  • Nicola Edwards
  • Andrew J M Boulton
  • Frank L Bowling
  • S Tawqeer Rashid
  • Fiona L Wilkinson
  • M Yvonne Alexander

Colleges, School and Institutes

External organisations

  • Cardiovascular Science, The Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
  • Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Kuala Lumpur, Malaysia; Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Kuala Lumpur, Malaysia.
  • Nephrology Department, Central Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  • 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.

Details

Original languageEnglish
Article number2309
Number of pages12
JournalScientific Reports
Volume9
Issue number1
Publication statusPublished - 19 Feb 2019

Keywords

  • Endothelial colony forming cells, endothelial progenitor cells, diabetes, glycomimetic, neuropathic and neuroischemic foot ulcers, angiogenesis and mitochondrial function

ASJC Scopus subject areas