粘附分子在造血干细胞归巢中的作用

造血干细胞 (Hematopoietic stem cell,HSC)的归巢类似于炎性细胞向炎症部位的归巢 ,是一个高度选择的过程。从 HSC移植治疗白血病中发现 ,成功的骨髓移植要求 HSC能归巢 (Homing)至骨髓 ,即 :离开外周血液循环准确进入骨髓腔血管外的龛 (Niche)中。所以 ,研究造血干细胞归巢具有重要的意义。但是 ,归巢机制尚不十分清楚。根据已有的研究显示 ,HSC归巢的过程是多步骤粘附的级联放大作用介导的 ,涉及许多分子参与的过程。包括 :1 HSC跨越骨髓内皮细胞 (Endothelial cell,EC)迁入髓腔 ;2 HSC与骨髓造血微环境中的基质细胞和基质相互…     

造血干细胞归巢机制研究进展

造血干细胞(hemopoietic stem cell,HSC)移植已经成为治疗难治性血液病、免疫缺陷性疾病、恶性肿瘤等的重要手段之一,外周血干细胞移植由于干细胞采集方便,移植后造血重建快等优点得到广泛应用,而影响外周血干细胞移植能否成功最重要因素取决于干细胞数量、干细胞能否顺利归巢、植入.造血干细胞归巢(homing)是指定向造血干细胞通过静脉移植经外周血循环进入受体后,经复杂的分子间相互作用而介导其在骨髓内识别与定位[1].目前研究表明,HSC归巢包括一系列复杂的过程:(1)移植的干细胞滚动粘附于骨髓血窦内皮;(2)稳定的黏附并穿行内皮;(3)到达血管外骨髓微环境开始增殖分化,重建造血[2].现就干细胞归巢的过程及其相关机制进展综述如下.     

黄芪在外周血造血干细胞移植中应用的初步实验研究

目的：为研究中药黄芪对外周血造血干细胞移植术后早期造血功能重建有无促进作用。方法：以致死量辐照并行外周血造血干细胞移植的BALB/c小鼠为模型,移植后给予黄芪注射液10g/kg或20g/kg腹腔注射,连续15天,观察4周内外周血象的恢复情况,并对骨髓造血微环境行透射电镜观察。结果：黄芪组小鼠外周血白细胞的恢复快于对照组,血小板的恢复与对照组无显著差异,两个黄芪剂量组之间无显著差异;电镜检查发现黄芪组小鼠骨髓中内皮细胞、肉状细胞的损伤轻于对照组,内皮细胞、网状细胞与造血原始细胞之间的接角度较对照组紧密。结论：黄芪能促进小鼠外周血造血干细胞移植术后早期白细胞的重建,其机理可能是通过保护和改善凡髓造血微环境,改善骨髓基质细胞与造血干细胞之间接触,并促进G-CSF等内源性细胞因子的分泌。     

卵黄囊造血的研究进展

卵黄囊是哺乳动物发育过程中最早的造血器官，同时还是最早形成血管的地方。胚胎的红系造血首先是在卵黄囊的血岛中发现，哺乳动物卵黄囊中包含多潜能的前体细胞即卵黄囊造血干细胞（Yolk sac hemopoietic stemcells，YS—HSC），不仅能分化成胚胎原始有核红细胞，体外实验证明还能产生成熟红细胞、淋巴细胞和髓系细胞等定向血细胞系；动物实验亦证实YS—HSC具有长期重建造血能力。最近有研究发现卵黄囊造血干细胞可能是成人造血干细胞的来源。     

外周血造血干细胞动员方式研究进展

外周造血干细胞(peripheral blood stem cells,PBSC)的动员是一个复杂的多因素、多步骤过程,细胞与细胞间、细胞与基质间以及细胞内的信号传导途径构成网状联络,影响着造血干细胞的增殖、迁移、分化、凋亡和归巢各阶段.近年来,关于造血干细胞动员方式的研究发展迅速,现综述其最新进展.     

造血干细胞移植治疗多发性骨髓瘤的研究进展

多发性骨髓瘤(MM)是浆细胞恶性克隆性疾病,造血干细胞移植治疗MM患者的疗效明显优于传统化疗,是初治MM患者的标准治疗方案。造血干细胞移植包括自体干细胞移值、异基因造血干细胞移植(包括清髓性异基因造血干细胞移植及非清髓异基因造血干细胞移植)。本文就造血干细胞移植治疗MM的疗效、预后因素、预处理方案、移植时机及二次移植等问题的研究进展进行了阐述。     

不同类型急性白血病患者骨髓间充质干细胞的病理学特征

骨髓间充质干细胞（MSC）具有在体内和体外支持造血的功能，因此联合MSC的造血干细胞移植有可能增强移植效果，最近研究结果证实联合MSC的造血干细胞移植可以促进造血干细胞的植入和造血恢复。既往研究发现急性白血病患者骨髓造血微环境存在病理改变，包括细胞的组成和功能改变。但是，急性白血病患者骨髓MSC是否受到影响以及影响程度，尚不清楚。此外，MSC的来源有限，而且异基因MSC存在归巢效率低等问题。     

造血干细胞移植治疗多发性骨髓瘤的研究进展

多发性骨髓瘤（MM）是浆细胞恶性克隆性疾病,造血干细胞移植治疗MM患者的疗效明显优于传统化疗,是初治MM患者的标准治疗方案。造血干细胞移植包括自体干细胞移值、异基因造血干细胞移植（包括清髓性异基因造血干细胞移植及非清髓异基因造血干细胞移植）。本文就造血干细胞移植治疗MM的疗效、预后因素、预处理方案、移植时机及二次移植等问题的研究进展进行了阐述。     

造血干细胞的发生和迁移

造血干细胞是造血系统细胞的鼻祖 ,它具有向各种髓细胞和淋巴细胞发育的潜能 ,也具有一定的自我更新能力。胚胎第 3周 ,血岛中央细胞分化为造血干细胞 ,然后经血流迁移入肝和脾 ,并开始造血 ,最后造血干细胞定居在红骨髓内造血 ,可产生红细胞、粒细胞、单核细胞和血小板 ,并可通过移植重建受损害的造血和免疫系统。1　造血干细胞的发生根据细胞发育的连续性 ,多能的造血干细胞只是干细胞池的一个发育阶段 ,它来自全能干细胞 ,又通过增殖分化逐渐减弱其自我更新和分化潜能 ,最终失去干细胞特征 ,成为没有自我更新能力和发育方向限定的造血祖…     

造血干细胞自我更新相关基因的研究进展

在机体的一生中,由小部分全能造血干细胞来产生祖细胞与成熟血细胞。为了在如此长的时期内维持造血,造血干细胞（HSCs）具备平衡定向分化与自我更新的能力是至关重要的。自我更新指由亲代细胞分裂而成的两个子代细胞,其中一个保留造血干细胞全部生物学特征,从而维持干细胞池的大小,即干细胞数量与质量的恒定。具备自我更新能力是HSCs的标志性特征,但该过程发生与调控的分子机制尚不明确。在本文中,笔者将综述最近发表的文献,即对影响HSCs自我更新的基因的过表达或敲除的研究,总结目前已知的HSCs自我更新的分子调控子及这些途径相互作用的可能方式。     

内皮祖细胞与高血压关系的研究进展

血管内皮结构与功能完整使心血管系统处在稳态状态。内皮受损且修复功能受限可导致许多心血管疾病的发生、发展。内皮祖细胞（EPCs）是血管内皮细胞前体细胞,在维持内皮稳态,促进血管内皮修复方面发挥重要作用。近年来对EPCs的研究发现,其与高血压病发生、发展有密切联系,其数量减少和功能紊乱都可能导致人类患高血压病风险增高。而高血压作为独立危险因素对血管内皮祖细胞有损伤作用。该文对EPCs与高血压关系的研究进展进行综述。     

Biological behaviour and role of endothelial progenitor cells in vascular diseases

Objective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007. The search term was “endothelial progenitor cells”.Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow, peripheral blood and adventitia can differentiate into mature endothelial cells (ECs). The progenitor cells, which express certain surface markers including AC133, CD34 and KDR, enable restoration of the microcirculation and ECs when injury or ischaemia occurs. Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development. Moreover, their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors. Impairment of the progenitor cells might limit the regenerative capacity, even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases. However, many challenges remain in understanding differentiation of endothelial progenitor cells, their mobilization and revascularization.     

妊娠高血压综合征患者循环内皮祖细胞功能的研究

目的研究妊娠高血压综合征患者循环内皮祖细胞功能的变化。方法选择2010年10月～2011年8月于我院产科住院的妊娠高血压综合征患者12例作为研究对象（妊娠高血压综合征组）,同时选取12例正常妊娠的同期入院患者作为对照组。分离两组患者外周血单个核细胞进行体外诱导培养以获得内皮祖细胞,并对其增殖、黏附、迁移能力进行检测。结果各组骨髓单个核细胞在体外培养下均能够获得内皮祖细胞．与对照组比较,妊娠高血压综合征组内皮祖细胞增殖、黏附、迁移能力均有不同程度的下降。结论妊娠高血压综合征的发生与循环内皮祖细胞功能的下调存在明显的相关性。     

Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was ＂endothelial progenitor cells＂.Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.     

内皮祖细胞在冠心病中的应用

内皮祖细胞（EPCs）是内皮细胞的前体细胞,能修复血管内皮细胞、促进内皮功能恢复,近年来在心血管领域中越来越受到人们的关注。本文就内皮祖细胞存在的证据、生物学特性、动员及在冠心病中的应用进行综述。     

血管内皮祖细胞治疗缺血性心脏病的研究进展

内皮祖细胞是内皮细胞的前体细胞,是一类能够迁移、增殖,并分化为成熟血管内皮细胞的前体细胞,属于干细胞群体,参与人胚胎血管生成及出生后血管新生和内皮损伤后的修复过程,还可在一定条件下分化为心肌细胞。近年来的研究表明其与冠心病发生、发展及治疗的关系密切,为冠心病治疗提供了新思路。本文就内皮祖细胞的生物学特性及其在缺血性心脏病中的临床研究现状予以综述。     

内皮细胞对小鼠粒系、红系和巨核系造血的调控作用

目的 了解内皮细胞对小鼠粒系、红系和巨核和造血功能的影响。为进一步研究血发生及其调控提供理论依据。方法 取剖腹产术后12小时以内的人脐静脉内皮细胞,按Jaffe法进行培养,建立内皮细胞体外细胞体外培养模型。而后收集原代培养的内皮细胞上清液,应用造血祖细胞体外培养方法进行体外粒-单系祖细胞克隆形成胞克隆形成单位（CFU-MK）单固体培养。结果 在有内皮细胞上清液存在的各培养体系中,集落形成良好,而在同样培养条件下,在无内皮细胞上清液存在的体系中,需加入外源性的GM-CSF、EPO和IL-3才能表现出对粒系、红系和巨核系造血的刺激作用。结论 （1）内皮细胞能够通过分泌造血生长因子,支持各系祖细胞的增殖与分化;（2）内皮细胞上清液可作为标准的生长因子来源,用于体外干细胞的扩增和某些血液病的治疗;（3）内皮细胞和造血干细胞/祖细胞的相互作用在体内的造血调控中也可能起了重要作用;（4）在内皮细胞上清液中可能含有尚未能证明的其他造血生长因子,这些因子单独或协同地发挥作用。支持了各系祖细胞的增殖。     

Inducing effects of macrophage stimulating protein on the expansion of early hematopoietic progenitor cells in liquid culture

Background Macrophage stimulating protein （MSP） is produced by human bone marrow endothelial cells. In this study we sought to observe its effects on inducing the expansion of early hematopoietic progenitor cells which were cultured in a liquid culture system in the presence of the combination of stem cell factor （SCF）, interleukin 3 （IL-3）, interleukin 6 （IL-6）, granulocyte macrophage-colony stimulating factor （GM-CSF）, erythropoietin （EPO） （Cys） and MSP or of Cys and bone marrow endothelial cell conditioned medium （EC-CM）. Methods Human bone marrow CD34^＋ cells were separated and cultured in a liquid culture system for 6 days. Granulocyte-macrophage colony forming unit （CFU-GM） and colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte （CFU-GEMM） were employed to assay the effects of different treatment on the proliferation of hematopoeitic stem/progenitor cells. The nitroblue tetrazolium （NBT） reductive test and hoechest 33258 staining were employed to reflect the differentiation and apoptosis of the cells respectively. Results MSP inhibited the proliferation of CFU-GM and CFU-GEMM in semi-solid culture and the inhibitory effect on CFU-GEMM was stronger than on CFU-GM. MSP inhibited the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators. Bone marrow （BM） CFU-GEMM was 2.3-fold or 1.7-fold increase or significantly decreased in either Cys＋EC-CM, Cys＋MSP or Cys compared with 0 hour control in liquid culture system after 6 days. Conclusion MSP, a hematopoietic inhibitor, inhibits the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators and makes the early hematopoietic progenitor cells expand in a liquid culture system.     

内皮祖细胞与冠心病的研究

内皮祖细胞是内皮细胞的前体细胞,是一类能够迁移、增殖,并分化为成熟血管内皮细胞的前体细胞,其参与人胚胎血管生成,及出生后血管新生和内皮损伤后的修复过程。近年来的研究表明其与冠心病发生、发展及治疗的关系密切,为冠心病治疗提供了新思路。现就内皮祖细胞的生物学特性及其在冠心病中的研究现状做一综述。     

Differences in the primary culture, purification and biological characteristics between endothelial cells and smooth muscle cells from rat aorta

Objective: To investigate the differences of primary culture, purification and biological characteristics between endothelial cells and smooth muscle cells from rat aorta. Methods: Endothelial cells were obtained using the vascular ring adherence, collagenase digestion method and an improved vascular ring adherence method, while smooth muscle cells were separated from tissue sections of rat aorta. Clones of endothelial cells were selected by limiting dilution assay. Both cell types were identified using specific cell immunofluorescent markers,and phase contrast microscopy was used to observe the morphological disparity between endothelial cells and smooth muscle cells at the single cell and colony level. Cell proliferation was determined by the cell counting kit-8. Differences between endothelial cells and smooth muscle cells were evaluated in trypsin digestion 6me, attachment time and recovery after cryopreservation. Results: Endothelial cells were obtained by all three methods. The improved vascular ring method provided the most reproducible results. Cells were in good condition, and of high purity. Smooth muscle cells were cultured successfully by the tissue fragment culture method. Clonal expansion of singleendothelial cells was attained. The two cell types expressed their respective specific markers, and the rate of proliferation of smooth muscle cells exceeded that of endothelial cells. Endothelial cells were more sensitive to trypsin digestion than smooth muscle cells. In addition, they had a shorter adherence time and better recovery following cryopreservation than smooth muscle cells. Conclusion: The improved vascular ring method was optimal for yielding endothelial cells. Limiting dilution is a novel and valid method for purifying primary endothelial cells from rat aorta. Primary rat endothelial cell and vascular smooth muscle cell cultures exhibited different morphological characteristics, proliferation rate, adherence time, susceptibility to trypsin digestion and recovery after cryopreservation. Our research can be a good foundation for further application in the regeneration of blood vessel.