血管形成中细胞因子对内皮祖细胞作用的研究进展

内皮祖细胞在缺血组织的血管形成及损伤血管的内皮再生中起重要作用.细胞因子作为血管形成中微环境的重要组成,对内皮祖细胞的调控发挥重要作用,有效应用对内皮祖细胞发挥正性调控作用的细胞因子可明显提高内皮祖细胞的数量、生物学功能及其治疗效果.现就血管内皮生长因子等7种细胞因子对内皮祖细胞的调控机制进行综述.     

CXCR4信号通路介导5型磷酸二酯酶抑制剂他达拉非对内皮祖细胞的保护作用

现有的研究认为，来源于骨髓的内皮祖细胞（EPC）可通过生成内皮细胞参与体内新生血管形成。内皮祖细胞一旦释放人血液循环，将定殖于血管损伤部位，并参与血管内皮的再生与修复。     

内皮祖细胞在下肢血管疾病研究中的新进展

内皮祖细胞是内皮细胞的前体细胞,在某些生理、病理状态下,可随血液流至相应组织,分化为内皮细胞,进一步促进血管的生成。内皮祖细胞参与血管新生,对于创伤修复、缺血性疾病的治疗以及肿瘤的靶向治疗具有重要意义,在临床上具有广阔的应用前景。下肢缺血性疾病,特别是慢性下肢缺血性疾病是临床工作比较棘手的问题,近些年发病率逐年上升,严重影响患者生活质量,然而很多药物对该病效果欠佳。间充质细胞,特别是具有诱导血管新生的内皮祖细胞试验性应用于临床,以其对缓解慢性下肢缺血性疾病的症状(缺血下肢行走时间延长、静息痛减轻、踝肱指数增加),促进下肢缺血区域血管新生的作用,给治疗慢性下肢缺血性疾病带来了新的希望。     

内皮祖细胞在治疗下肢缺血性疾病中的研究进展

随着人口老龄化、饮食结构改变及引起血管疾病高危因素的增加,下肢缺血性疾病已成为老年人的多发病,是截肢致残的主要原因.作为21世纪最先进的技术,干细胞移植快速地应用于临床,并被认为可能是根治性治疗下肢缺血性疾病的方法之一,内皮祖细胞由于其独特的生物学特性逐渐成为治疗这一病变的新方向和新研究热点.本文着重介绍内皮祖细胞治疗肢体缺血性病变的理论基础和研究进展.     

内皮祖细胞治疗下肢缺血性疾病的相关机制进展

本文介绍内皮祖细胞的定义,并对内皮祖细胞治疗下肢缺血性疾病的四种机制:血管发生(vasculogenesis)、血管生成(angiogenesis)、动脉形成(arteriogenesis)和旁分泌(paracrine mechanisms)等相关机制做一阐述.     

骨髓细胞移植治疗肢体缺血的研究进展

严重的慢性缺血性疾病临床治疗相当棘手 ,“治疗性的血管新生”是很有前景的治疗方案 ,即应用血管生长因子或其基因 ,促进缺血组织周围的血管新生和侧肢循环建立 ,改善局部组织供血。新近研究表明 ,这种血管生长因子的促血管新生作用 ,其实质是通过动员骨髓中血管内皮的前体细胞—内皮祖细胞(EPC) ,向缺血组织游走并分化为内皮细胞 (EC) ,而发挥其血管新生效应[1] 。这种骨髓来源的EPC有望在不久的将来成为重症缺血性疾病新的治疗靶点 ,已迅速成为国内外的研究热点。一、内皮祖细胞与血管新生1.内皮祖细胞的起源和分布 :胚胎时期的血管…     

内皮祖细胞与缺血性疾病治疗

血管内皮细胞损伤和功能障碍是动脉硬化发生的重要促进因素。外周循环来源于骨髓的内皮祖细胞(EPC),对血管损伤后再内皮化和促进缺血组织内源性血管形成起重要作用。这些结果提示EPC与缺血性疾病发生有密切关系。一、EPC数量与缺血性疾病关系血管内皮完整性体现了内皮细胞损伤程度和修复能力的平衡。过去认为,内皮细胞修复主要依赖周围内皮细胞移行和增生。但内皮细胞是终末分化细     

内皮祖细胞与肾脏缺血再灌注损伤

内皮祖细胞是血管内皮细胞的前体细胞,在某些损伤因素刺激下,可从骨髓动员到外周血参与损伤血管的修复,对肾脏缺血再灌注损伤产生了重要影响,引起了国内外学者的关注.本文就内皮祖细胞在肾缺血再灌注损伤中的研究进展作一综述.     

兔外周血内皮祖细胞的分离培养及鉴定

内皮细胞(EC)构成正常的血管壁,内皮祖细胞(EPCs)是EC的前体细胞,可在体内、外分化为成熟EC。本研究以新西兰兔外周血为研究对象,探索分离、培养、扩增EPCs的方法,以期为细胞治疗为主的血管性疾病治疗提供实验基础。     

毛细血管渗漏综合征中内皮祖细胞的作用

体外循环后毛细血管渗漏综合征的血管修复对该病的恢复起到至关重要的作用。外周血中存在着能分化为血管内皮细胞的内皮祖细胞,能够促进损伤血管修复和生后血管再生。血浆中的血管内皮生长因子（VEGF）、促红细胞生成素（EPO）等因子通过刺激血管内皮祖细胞的动员、迁移、黏附和分化,促进血管修复和再生。现对体外循环后血管内皮祖细胞的数量和功能情况及其与血浆相关因子的相互作用进行综述,旨在为毛细血管渗漏综合征的治疗和预防提供新的思路.     

血管内皮生长因子与治疗性血管生成研究进展

血管内皮生长因子(vascular endothelial growtll factor,VEGF)是内皮细胞特异的有丝分裂原,有促进内皮细胞增生、增强血管通透性、加速新血管形成的作用.血管生成是一个具有重要生理、病理意义的过程.在人体的创伤愈合、炎症反应、器官再生过程以及肿瘤生长转移、血管增生性疾病中,血管生成有重要作用.治疗性血管生成是指利用成血管诱导因子或内皮祖细胞,模拟体内血管生成机制,促进新生血管形成,改善侧支循环.本文就VEGF和治疗性血管生成研究进展做一综述.     

Endothelial progenitor cells promote astrogliosis following spinal cord injury through Jagged1-dependent Notch signaling

Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.     

Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells

OBJECTIVE: Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting. METHODS: Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion. RESULTS: Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients. CONCLUSIONS: Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.     

Circulating endothelial progenitor cells in subjects with erectile dysfunction

Erectile dysfunction (ED) is often the first clinical sign of endothelial dysfunction and may precede overt cardiovascular diseases. Bone marrow-derived endothelial progenitor cells migrate into the peripheral circulation to promote endothelial repair. The number of circulating progenitor cells is reduced in patients with cardiovascular risk factor. The objective of our study was to determine the number of these cells in patients with ED both with and without cardiovascular risk factors. These subjects have lower number of circulating progenitor cells, confirming the existence of an endothelial dysfunction and supplying the evidence that ED may be the first symptom of an endothelial damage.     

Zirkulierende Vorl?uferzellen

The existence of circulating cells, endothelial progenitor cells (EPC), in peripheral blood was first demonstrated in 1997. Under pathological conditions EPCs are mobilized from the bone marrow. A variety of factors which stimulate mobilization were identified, including granulocyte colony stimulating factor, vascular endothelial growth factor (VEGF) and interleukin 8. Endothelial progenitor cells participate in remodelling processes of the vascular walls by clustering in areas of endothelial damage and reducing the formation and hyperplasia of neointima and atherosclerotic plaques. This discovery allowed new approaches in the treatment of peripheral arterial occlusive disease. In most studies an improvement in perfusion of tissues and a reduction of the amputation rate have been observed following transplantation of EPCs but the results did not live up to expectations. With respect to clinical benefits the supportive application for vascular interventions, in addition to the development and colonization of suitable synthetic prosthetic materials and the benefits for tissue engineering look very promising.     

大鼠脐血来源单个核细胞诱导为内皮祖细胞的免疫荧光检测

目的脐血（umbilical cord blood,UCB）中含有大量内皮祖细胞（endothelial progenitor cells,EPCs）,内皮祖细胞（EPCs）是血管内皮细胞的前体细胞,有分化为血管内皮细胞的能力,为骨组织工程血管化带来新的途径。本实验研究大鼠脐血来源的单个核细胞体外诱导为EPCs的可能性。方法分离大鼠脐血单个核细胞,血管内皮诱导液（添加10％胎牛血清,1％青霉素,1％链霉素,VEGF20ug／L,IGF-12ug／L,bFGF2ug／L,EGF20ug／L）培养分化,于3周、6周进行免疫荧光染色检测贴壁细胞CD34、CD133、Flk-1、vWF表面标志。结果培养三周单个核细胞CD34、CD133、Flk-1、vWF抗体免疫荧光检测均为阳性;六周免疫荧光染色可见CD34、Flk-1、VWF组为阳性,CD133组部分为阳性,阴性对照组未发现阳性细胞。结论大鼠脐血来源的单个核细胞在体外诱导3周可以分化为EPCs,6周部分细胞分化为成熟血管内皮细胞。     

Circulating inflammatory endothelial cells contribute to endothelial progenitor cell dysfunction in patients with vasculitis and kidney involvement

Impaired angiogenic function has been reported in patients with kidney failure. During vascular damage, endothelial cells may detach from the site of inflammation and be released into the peripheral blood. With the use of Wegener's granulomatosis as a study model, whether circulating inflammatory endothelial cells (IEC) can (1) be used as a disease activity marker and (2) contribute to sustained vascular damage by inducing endothelial progenitor cell (EPC) dysfunction were examined. IEC-defined as endothelial cells that express the two inflammatory-associated markers vascular-adhesion protein-1 (VAP-1) and MHC class I-related chain A (MICA)-were increased significantly in patients with active disease as compared with those in remission. IEC expressed high levels of inducible nitric oxide synthase and neutrophil-activating chemokines, such as macrophage inflammatory protein-1alpha, growth-related oncogene-alpha, epithelial neutrophil activating peptide-78, and IL-8, and induced increased neutrophil migration. IEC levels significantly correlated with C-reactive protein and extent of organ involvement. Patients with active disease had decreased numbers of EPC colony-forming units and a high expression of VAP-1 and MICA in kidney endothelium. EPC did not express VAP-1 or MICA. IEC significantly inhibited proliferation, migration, and endothelial nitric oxide synthase expression in EPC. Thus, apart from being a new disease activity marker, IEC may contribute to vascular damage by impairing the functional capacity for repair by EPC. IEC may provide a unique in vitro system to study pathogenesis of kidney and vascular diseases.     

Galectin-3对外周血内皮祖细胞源性血管内皮细胞增殖能力的影响

目的观察重组人半乳糖凝集素-3(Galectin-3)对外周血内皮祖细胞源性血管内皮细胞增殖能力的影响。方法提取人外周血内皮祖细胞,将其定向诱导为成熟血管内皮细胞,加入不同终浓度的Galectin-3进行培养,观察不同浓度Galectin-3对外周血内皮祖细胞源性内皮细胞增殖能力的影响。结果 0.1、1.0、2.5、5.0和10.0μg/ml浓度组外周血内皮祖细胞源性内皮细胞的增殖能力均高于0μg/ml组,其中0.1,1.0及2.5μg/ml浓度组与0μg/ml组比较差异无统计学意义(P>0.05),而5.0及10.0μg/ml组细胞增殖能力明显高于0、0.1、1.0及2.5μg/ml组,差异有统计学意义(P<0.05),10.0μg/ml浓度组细胞增殖能力又明显高于5.0μg/ml浓度组,差异有统计学意义(P<0.05)。结论 Galectin-3可促进体外培养的外周血内皮祖细胞源性血管内皮细胞的增殖能力。     

Bone marrow-derived cells and arterial disease

This article reviews the association between bone and artery disease, with particular relevance to progenitor cells. The review was based on insight gained by analysis of previous publications and on-going work by the authors. A large number of studies have demonstrated a correlation between bone pathology, particularly osteoporosis, and atherosclerosis. In this review we highlight the particular aspect of bone marrow progenitor cells in the bone-artery link. Progenitor cells, primarily those believed to give rise to endothelial cells, have been inversely correlated with atherosclerosis severity and risk factors. Therapeutic approaches aimed at manipulating progenitor cells in revascularization and vascular repair have demonstrated some promising results. Subtypes of progenitor cells have also been linked with vascular pathology, however, and further studies are required to assess relative beneficial and pathologic effects of bone marrow-derived progenitors. Further understanding of the link between bone and artery pathophysiology is likely to be of significant value in developing new therapies for vascular disease.