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

Research output: Contribution to journalArticlepeer-review

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Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics. / Langford-Smith, Alexander W W; Hasan, Ahmad; Weston, Ria; Edwards, Nicola; Jones, Alan M; Boulton, Andrew J M; Bowling, Frank L; Rashid, S Tawqeer; Wilkinson, Fiona L; Alexander, M Yvonne.

In: Scientific Reports, Vol. 9, No. 1, 2309, 19.02.2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Langford-Smith, AWW, Hasan, A, Weston, R, Edwards, N, Jones, AM, Boulton, AJM, Bowling, FL, Rashid, ST, Wilkinson, FL & Alexander, MY 2019, 'Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics', Scientific Reports, vol. 9, no. 1, 2309. https://doi.org/10.1038/s41598-019-38921-z

APA

Langford-Smith, A. W. W., Hasan, A., Weston, R., Edwards, N., Jones, A. M., Boulton, A. J. M., Bowling, F. L., Rashid, S. T., Wilkinson, F. L., & Alexander, M. Y. (2019). Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics. Scientific Reports, 9(1), [2309]. https://doi.org/10.1038/s41598-019-38921-z

Vancouver

Author

Langford-Smith, Alexander W W ; Hasan, Ahmad ; Weston, Ria ; Edwards, Nicola ; Jones, Alan M ; Boulton, Andrew J M ; Bowling, Frank L ; Rashid, S Tawqeer ; Wilkinson, Fiona L ; Alexander, M Yvonne. / Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics. In: Scientific Reports. 2019 ; Vol. 9, No. 1.

Bibtex

@article{357365ea77c44dd5b5fcbf7e0a780ab8,
title = "Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics",
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.",
keywords = "Endothelial colony forming cells, endothelial progenitor cells, diabetes, glycomimetic, neuropathic and neuroischemic foot ulcers, angiogenesis and mitochondrial function",
author = "Langford-Smith, {Alexander W W} and Ahmad Hasan and Ria Weston and Nicola Edwards and Jones, {Alan M} and Boulton, {Andrew J M} and Bowling, {Frank L} and Rashid, {S Tawqeer} and Wilkinson, {Fiona L} and Alexander, {M Yvonne}",
year = "2019",
month = feb,
day = "19",
doi = "10.1038/s41598-019-38921-z",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Diabetic Endothelial colony forming cells have the potential for restoration with glycomimetics

AU - Langford-Smith, Alexander W W

AU - Hasan, Ahmad

AU - Weston, Ria

AU - Edwards, Nicola

AU - Jones, Alan M

AU - Boulton, Andrew J M

AU - Bowling, Frank L

AU - Rashid, S Tawqeer

AU - Wilkinson, Fiona L

AU - Alexander, M Yvonne

PY - 2019/2/19

Y1 - 2019/2/19

N2 - 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.

AB - 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.

KW - Endothelial colony forming cells

KW - endothelial progenitor cells

KW - diabetes

KW - glycomimetic

KW - neuropathic and neuroischemic foot ulcers

KW - angiogenesis and mitochondrial function

UR - https://doi.org/10.1038/s41598-019-38921-z

UR - http://www.scopus.com/inward/record.url?scp=85061769452&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-38921-z

DO - 10.1038/s41598-019-38921-z

M3 - Article

C2 - 30783159

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 2309

ER -