内皮前体细胞及其与肺疾病关系的研究进展

内皮前体细胞存在于骨髓、外周血和脐带血中,可以分化为成熟的内皮细胞.不仅参与胚胎期的血管发育,也在成年的血管新生中起作用.肺部疾病尤其是炎症性疾病,几乎都存在血管内皮的损伤与修复机制.本文就内皮前体细胞的来源、生物学特征和功能,及其在肺疾病中的研究进展进行概述.     

内皮祖细胞在肺动脉高压的作用

内皮祖细胞是成熟血管内皮细胞的前体细胞,属于干细胞群体,其在血管再生与修复方面的应用越来越受到关注.肺动脉高压作为一种致死性很高的肺血管疾病,其发病与血管内皮损伤密切相关.目前的研究证实,内皮祖细胞在肺动脉高压血管内皮修复中具有重要作用,内皮祖细胞移植有可能成为临床治疗肺动脉高压的一种有效手段.     

内皮祖细胞移植策略研究进展

内皮祖细胞是内皮细胞的前体细胞,是成年个体中与血管新生关系最为紧密的干细胞成分,大量动物实验和初步临床研究均显示其在治疗缺血性心脏病、外周缺血性血管疾病及血管损伤后再狭窄等方面具有广阔的临床应用前景。现主要对近年来内皮祖细胞移植策略做一综述。     

内皮前体细胞与肺动脉高压

内皮损害和内皮功能障碍是肺动脉高压病理改变的核心环节,而循环中内皮前体细胞在一定的条件下可向内皮细胞分化,促进内皮增生以及新生成血管。循环中内皮前体细胞既可作为肺动脉高压发生的生物标志物,也具有一定程度的治疗作用。     

内皮祖细胞与缺血性心血管病

内皮祖细胞(EPCS)是一种能分化为血管内皮细胞的前体细胞,也称为成血管母细胞,是一种成体干细胞.近期研究发现,EPCS不仅参与胚胎血管生成(vascuLlogenesis),也参与出生后的血管新生(angiogenesis),提示EPCS在缺血性疾病中可能有重要意义. 　　……     

内皮祖细胞与PI3K/Akt信号传导通路

内皮祖细胞作为内皮的前体细胞,主要来源于骨髓,在成人受损血管的修复、新生血管发生/生成中起重要作用.多种伴有血管内皮细胞损伤的疾病都可引起外周血循环、内皮祖细胞数量、功能的变化.因此,内皮祖细胞功能的研究,日益为人们所关注.研究显示PI3K/Akt信号传导通路在内皮祖细胞的动员、迁移、归巢、分化、抗凋亡上发挥重要作用.现主要就内皮祖细胞与PI3K/Akt信号传导通路关系作一综述.     

生长因子的协同作用与新血管形成的研究进展

缺血性疾病的血管重建不只依赖于血管新生,还需骨髓来源的前体细胞的参与.缺血本身不仅能动员血管前体细胞,而且能够增强它们向内皮细胞分化的能力.有许多生长因子如血管内皮生长因子、血小板源性生长因子等能募集骨髓来源的内皮前体细胞到血管重建部位.但是,缺血诱导的血管形成往往不能完全弥补外周血管病变和动脉闭塞所引起的血流减少,并且单一的生长因子作用也不能诱导成熟稳定的血管形成,同时易出现并发症而制约了其临床应用.因此如何利用生长因子动员血管前体细胞参与血管新生,并通过其协同作用形成稳定的功能性的血管成为研究的热点.本文就生长因子协同作用参与新血管形成方面作一综述.     

内皮前体细胞移植:冠心病治疗的新策略

干细胞研究的进展和基因治疗技术在心血管的应用为缺血性心脏病的治疗提供了新策略。基因修饰后内皮前体细胞移植既补充了功能不良且数量不足的内皮前体细胞又诱导并促进了局部新血管的生成 ,展示了美好的临床应用前景。本文回顾了近几年来缺血性心脏病治疗的新概念 ,重点介绍了国外内皮前体细胞及其基因修饰应用的新进展 ,并对存在的问题和应用前景分别进行了讨论和展望     

内皮祖细胞在自身免疫病中的研究进展

内皮祖细胞(endothelial progenitor cells,EPCs)是一群起源于骨髓,存在于外周血,与来源于胚胎血岛细胞具有相似特征的单核细胞群.EPCs是血管内皮细胞的前体细胞,在特定的条件下分化为成熟的内皮细胞(ECs),参与成人体内的血管发生和血管再生.1997年,Asahara等[1]在外周血中首次发现EPCs的存在,因为它们在新血管形成和血管修复方面的重要作用,使之在血管相关疾病的研究中掀起了热潮.研究发现,这类细胞具有治疗多种人类疾病的潜能,主要包括心血管疾病、缺血性周围血管病、肿瘤和自身免疫病的治疗.本文对EPCs的生物学特性及其与自身免疫病的关系综述如下.     

内皮祖细胞与缺血性脑血管病的细胞治疗

内皮祖细胞(EPC)是血管内皮细胞的前体细胞,存在于骨髓、外周血和脐血中,并参与出生后的血管发生过程.内源性和外源性因素刺激可动员骨髓EPC进入外周血,参与缺血组织的血管重建和损伤血管的再内皮化过程.血液循环中的EPC数量或质量下降是缺血性卒中预后不良的重要原因之一.EPC移植有可能为缺血性脑血管病的治疗提供一种全新的治疗策略.     

内皮祖细胞来源外泌体在血管生成中作用的研究进展

内皮祖细胞最早在外周血中被发现,随着内皮祖细胞的相关研究不断丰富,发现内皮祖细胞也通过释放外泌体参与到了血管再生过程中。在缺血/再灌注损伤等疾病中,内皮祖细胞外泌体中的microRNA分子起到促进血管再生,以降低缺血/缺氧微环境带来的损伤风险并促进组织再生修复的作用。因此,内皮祖细胞外泌体已经被看作是血管再生的重要因素。本文就近年来内皮祖细胞来源外泌体在血管生成中作用的研究进展做一综述,以期为血管损伤相关疾病的治疗提供新思路。     

Progenitor cells in the pulmonary circulation

The mechanisms involved in the regulation of pulmonary vascular endothelial cells to replace aged or injured cells remains poorly understood, although differences in proliferative potential between the microvascular and macrovascular endothelium are well described. The presence of resident pulmonary vascular endothelial progenitor cells in rats and mice has been recently reported. These resident endothelial progenitor cells display clonal proliferative potential, restricted expression of cell surface molecules to those typical of lung endothelium, and in vivo vessel-forming ability upon transplantation into recipient animals. The rat pulmonary microvascular endothelium is enriched in resident progenitor cells, with the highest proliferative potential compared with the pulmonary macrovascular endothelium. Preliminary evidence suggests that resident endothelial progenitor cells are present in the human lung vasculature, but whether differences in enrichment of the progenitors in various pulmonary vascular beds exist remains to be determined.     

Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow

To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.     

Increased circulating endothelial progenitor cells are associated with survival in acute lung injury

RATIONALE: Repair of damaged endothelium is important in recovery from acute lung injury. In animal models, bone marrow-derived endothelial progenitor cells differentiate into mature endothelium and assist in repairing damaged vasculature. OBJECTIVES: The quantity of endothelial progenitor cells in patients with acute lung injury is unknown. We hypothesize that increased numbers of circulating endothelial progenitor cells will be associated with an improved outcome in acute lung injury and the acute respiratory distress syndrome. METHODS: Peripheral blood mononuclear cells from the buffy coat of patients with early acute lung injury (n=45), intubated control subjects (n=10), and healthy volunteers (n=7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were removed and replated on fibronectin-coated cellware at a concentration of 1x10(6) cells/well. Colony-forming units were counted after 7 days' incubation. MEASUREMENTS/MAIN RESULTS: Endothelial progenitor cell colony numbers were significantly higher in patients with acute lung injury compared with healthy control subjects (p<0.05), but did not differ between patients with acute lung injury and intubated control subjects. However, in the 45 patients with acute lung injury, improved survival correlated with a higher colony count (p<0.04). Patients with acute lung injury with a colony count of >or= 35 had a mortality of 30%, compared with 61% in those with colony counts <35 (p<0.03), results that persisted in a multivariable analysis correcting for age, sex, and severity of illness. CONCLUSIONS: An increased number of circulating endothelial progenitor cells in acute lung injury is associated with improved survival.     

Hemogenic endothelium during development and beyond

During embryonic development, multilineage HSCs/progenitor cells are derived from specialized endothelial cells, termed hemogenic endothelium, within the yolk sac, placenta, and aorta. Whether hemogenic endothelial cells contribute to blood cell development at other sites of definitive hematopoiesis, such as in the fetal liver and fetal bone marrow, is not known. Also unknown is whether such cells exist within the vasculature of adult bone marrow and generate hematopoietic stem cells after birth. These issues and their clinical relevance are discussed herein.     

Regenerative Cell and Tissue-based Therapies for Pulmonary Arterial Hypertension

Within the span of 2 decades, cell-based regenerative therapies for pulmonary arterial hypertension have progressed from bench-side hypotheses to clinical realities. Promising preclinical investigations that examined the therapeutic potential of endothelial progenitor cell and mesenchymal stem cell populations have demonstrated the safety and efficacy of these cell types and provided the foundation for first-in-man clinical trials. Moreover, these studies have improved our understanding of the therapeutic mechanisms by which stem/progenitor cells exert their regenerative functions. Ultimately, these discoveries have led to new applications for stem and progenitor cells including the autologous cell reseeding of decellularized or synthetic lung scaffolds. In this review, an overview of established and emerging cell and tissue regenerative therapies for pulmonary lung diseases are presented, along with discussion of recent advancements in the emerging field of repopulating decellularized or bioengineered lung scaffolds with stem/progenitor cells for allogeneic transplant.     

Circulating endothelial progenitor cells as a link between synovial vascularity and cardiovascular mortality in rheumatoid arthritis

Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). Most Western countries face high and ever-increasing rates of cardiovascular disease. Each year, more Americans are killed by heart disease than by cancer. Diseases of the heart alone cause 30% of all deaths, with other diseases of the cardiovascular system causing substantial further deaths and disability. Indeed, cardiovascular disease is the major cause of death and disability in the USA and most European countries. The development of the vascular systems requires an intricate interplay of molecules such as vascular endothelial growth factor and endothelial progenitor cells. A defective vascular repair/regeneration is thought to be responsible for propagation of atherosclerosis, a key feature of cardiovascular disease. This is partly attributed to a reduction in the circulating endothelial progenitor cells in peripheral blood. Patients with rheumatoid arthritis (RA) have a higher than average incidence of cardiovascular disease in comparison with the general population, with an increased risk of stroke and myocardial infarction, and an increased risk of fatality following myocardial infarction. This review focuses on the current evidence linking the role played by endothelial progenitor cells to the development of cardiovascular disease and why this might relate to the increased risk observed in RA patients.