Cardiovascular Science, The Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
Diabetes Research Group, University of Manchester, Manchester, UK.
Sci Rep. 2019 Feb 19;9(1):2309. doi: 10.1038/s41598-019-38921-z.
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.
内皮祖细胞（ECFC）在糖尿病中的功能受损，导致血管内皮修复不良，从而导致糖尿病足溃疡愈合受损。我们已经开发出具有针对内皮功能障碍的保护作用的新型糖模拟药物。我们研究了糖模拟物 C3 对糖尿病 ECFC 功能能力的影响。从健康对照者和患有神经缺血（NI）或神经病变（NP）足溃疡的糖尿病患者中分离出 ECFC。从功能上讲，糖尿病 ECFC 的集落形成延迟（p<0.02），增殖能力差异（p<0.001），NO 生物利用度降低（NI ECFC；p<0.05）。糖尿病 ECFC 的趋化性迁移和血管生成能力也降低（p<0.01 和 p<0.001），NP ECFC 的伤口闭合和管形成缺陷明显（p<0.01）。线粒体活性的差异模式很明显，NI 细胞的活性升高，NP 细胞的活性降低（p<0.05）。糖模拟物的应用改善了患者 ECFC 体外划痕伤口闭合（p<0.01），在 NI 细胞中最为明显（p<0.001），其中管形成（p<0.05）也得到改善。我们使用新型糖模拟物证明了 NI 细胞缺陷的恢复，但 NP 细胞没有，这对于治疗性细胞移植或作为 NI 患者的局部治疗可能是有利的，但对 NP 患者则不然。
