Fox A, Smythe J, Fisher N, Tyler M P H, McGrouther D A, Watt S M, Harris A L
Stem Cells and Immunotherapies, National Blood Service, NHS Blood and Transplant, Oxford, UK.
Br J Surg. 2008 Feb;95(2):244-51. doi: 10.1002/bjs.5913.
Bone marrow-derived endothelial progenitor cells (EPCs) have been detected in the peripheral blood of patients following thermal injury. EPCs migrate to sites of active neovascularization in response to mediators released after trauma, contributing to wound healing. The aim was to characterize levels and kinetics of EPCs in burned patients, then relate these to key mobilizing factors, vascular endothelial growth factor (VEGF) and the chemokine (C-X-C motif) ligand 12 (CXCL 12), and compare them with those in healthy subjects.
The study included 19 adult patients with superficial or full-thickness burns and 50 blood donor volunteer controls. EPCs, identified by cell surface markers CD45(dim/-), CD133+, CD144+ and VEGF receptor 2, were quantified by four-colour flow cytometry. Plasma VEGF and CXCL12 were measured using enzyme-linked immunosorbent assay.
Burned patients showed a rapid rise in EPC levels within 24 h, a ninefold increase compared with controls, returning to basal levels by 72 h. Body surface area burned correlated strongly with the degree of mobilization. EPC levels correlated significantly with rises in plasma VEGF and CXCL12.
Thermal injury induced a rapid rise in EPCs that was proportional to the extent of the burn and significantly correlated with levels of angiogenic cytokines. Such cytokines may be used to stimulate EPCs as a future therapeutic target in burned patients.
在热损伤患者的外周血中已检测到骨髓来源的内皮祖细胞(EPCs)。EPCs可响应创伤后释放的介质迁移至活跃的新生血管形成部位,促进伤口愈合。本研究旨在明确烧伤患者体内EPCs的水平及动力学变化,然后将这些变化与关键的动员因子——血管内皮生长因子(VEGF)和趋化因子(C-X-C基序)配体12(CXCL 12)相关联,并与健康受试者进行比较。
本研究纳入了19例浅表或全层烧伤的成年患者以及50名献血志愿者作为对照。通过细胞表面标志物CD45(弱阳性/阴性)、CD133+、CD144+和VEGF受体2鉴定的EPCs,采用四色流式细胞术进行定量分析。采用酶联免疫吸附测定法检测血浆VEGF和CXCL12。
烧伤患者在24小时内EPCs水平迅速升高,与对照组相比增加了9倍,至72小时恢复至基础水平。烧伤体表面积与动员程度密切相关。EPCs水平与血浆VEGF和CXCL12的升高显著相关。
热损伤导致EPCs迅速升高,升高程度与烧伤范围成正比,且与血管生成细胞因子水平显著相关。此类细胞因子未来可能作为刺激EPCs的治疗靶点用于烧伤患者。