Academic Unit of Mental Health and Clinical Neuroscience, Clinical Sciences Building, School of Medicine, The University of Nottingham, Hucknall Road, Nottingham, NG5 1PB, UK.
Stem Cell Rev Rep. 2023 Aug;19(6):1856-1869. doi: 10.1007/s12015-023-10544-y. Epub 2023 May 2.
Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65 years of age. For this, blood samples were collected once from healthy volunteers (HVs, n = 40) and four times (admission and days 7, 30 and 90 post-stroke) from participants with lacunar (n = 38) or cortical (n = 43) stroke. EPCs were counted with flow cytometry and defined as non-haematopoietic cells (CD45-) expressing markers for stemness (CD34 +), immaturity (CD133 +) and endothelial maturity (KDR +). Clonogenesis, tubulogenesis, migration and proliferation assays were performed as measures of EPC functionality. Biochemical profile of plasma inflammatory and angiogenic agents were studied using specific ELISAs. Primary outcome was disability or dependence on day 90 post-stroke, assessed by the modified Rankin Scale (mRS). Compared to HVs, EPC numbers were higher in stroke patients at all time points studied, reaching significance at baseline and day 30. No differences in EPC counts and functionality were observed between lacunar and cortical stroke groups at any time. Plasma endostatin, PDGF-BB, TNF-α and VEGF levels were higher in stroke patients vs HVs. Patient outcome, evaluated by mRS on day 90 post-stroke, did not correlate with EPC count or functionality. Baseline EPC counts may serve as a diagnostic marker for stroke but fail to distinguish between different stroke subtypes and predict post-stroke outcome.
衰老是内皮功能障碍的原因,并使个体易患缺血性中风(IS)。内皮祖细胞(EPCs)可修复内皮损伤并诱导缺血后新生血管形成。鉴于老年人中风的高发率,本研究探讨了 EPC 数量和功能的变化是否能可靠地预测年龄≥65 岁患者中风的类型或结局。为此,我们从健康志愿者(HVs,n=40)中采集一次血液样本,并从腔隙性(n=38)或皮质性(n=43)中风患者中采集四次(入院时以及中风后第 7、30 和 90 天)。我们通过流式细胞术计数 EPC,并将其定义为表达干细胞标志物(CD34+)、不成熟标志物(CD133+)和内皮成熟标志物(KDR+)的非造血细胞(CD45-)。克隆形成、管形成、迁移和增殖试验用于评估 EPC 功能。使用特定的 ELISA 研究了血浆炎症和血管生成因子的生化谱。主要结局是中风后第 90 天的残疾或依赖程度,通过改良 Rankin 量表(mRS)进行评估。与 HVs 相比,中风患者的 EPC 数量在所有研究时间点均较高,在基线和第 30 天达到显著水平。在任何时间点,腔隙性和皮质性中风组之间的 EPC 计数和功能均无差异。与 HVs 相比,中风患者的血浆内皮抑素、PDGF-BB、TNF-α和 VEGF 水平更高。通过中风后第 90 天的 mRS 评估的患者结局与 EPC 计数或功能无关。基线 EPC 计数可作为中风的诊断标志物,但无法区分不同的中风亚型并预测中风后的结局。