干细胞与心肌再生

由于成年心肌细胞通常不能再生,严重的心肌损伤会导致心肌不可逆的重构坏死, 从而发生心功能失调. 干细胞再生治疗为心肌再生提供了很好的策略. 为了寻找合适的干细胞类型, 促进心肌再生, 有效改善心功能, 需要更好地了解心肌修复和再生的分子基础. 已有研究发现多种干细胞可促进心肌再生. 描述了骨髓干细胞的促血管新生及心肌分化的能力在心梗治疗中的作用, 还讨论了心脏侧群干细胞以及诱导型多能干细胞在心肌再生中的作用和分子机制. 所阐述的最新数据有利于拓展干细胞治疗的有效潜能及临床影响.     

我校附属协和医院糖尿病足治疗研究取得重大突破

日前，由我校协和医院血管外科金毕教授等施行的自体骨髓干细胞移植治疗下肢缺血取得了重大进展．     

加拿大科学家用干细胞在实验鼠体内生成血管

<正>他们是利用人体骨髓干细胞在实验鼠身上生成新血管。这项成果有望应用于治疗人类外周动脉等疾病。论文发表在美国《血液》杂志上。研究人员从人体骨髓中提取干细胞,并从中分离出3种不同类型的"促血管生成干细胞",将处理过的干细胞注射到实验鼠循环系统中。研究人员事先已将这些实验鼠腿部的一动     

加拿大科学家用干细胞在实验鼠体内生成血管

他们是利用人体骨髓干细胞在实验鼠身上生成新血管。这项成果有望应用于治疗人类外周动脉等疾病。论文发表在美国《血液》杂志上。研究人员从人体骨髓中提取干细胞,并从中分离出3种不同类型的促血管生成干细胞,将处理过的于细胞注射到实验鼠循环系统中。     

血管内皮生长因子与急性白血病骨髓的血管新生

目的:探讨血管内皮生长因子(VEGF)在急性白血病及其骨髓的新生血管之间的关系,为白血病的治疗寻找新的治疗方法。方法:查阅总结近15年来国内外相关文献,对VEGF的性质作用特点以及与急性白血病的关系进行综述。结果:白血病细胞表达较高的VEGF,VEGF促使血管生成和内皮细胞增生,白血病细胞与骨髓新生血管之间存在密切的关系。结论:抗VEGF和抗新生血管治疗有可能成为治疗急性白血病的新的思路和方法。     

微血管密度与血管内皮生长因子受体-3在骨髓增生异常综合征患者中的表达及意义

目的检测骨髓增生异常综合征患者骨髓中微血管密度和血管内皮生长因子受体-3表达水平并探讨其临床意义。方法采用免疫组织化学染色检测54例骨髓增生异常综合症患者、20例非恶性血液病患者对照组骨髓组织中微血管密度和血管内皮生长因子受体-3表达水平,采用蛋白质印迹法检测上述研究对象骨髓单个核细胞中血管内皮生长因子受体-3蛋白表达水平,分析其与临床特征的相关性。结果骨髓增生异常综合症患者骨髓组织中微血管密度和血管内皮生长因子受体-3表达水平明显高于非恶性血液病对照组,差异具有统计学意义(P0.05),而骨髓增生异常综合症低危组、中危组及高危组中微血管密度与血管内皮生长因子受体-3的表达水平无显著差异(P0.05),经相关性分析微血管密度和血管内皮生长因子受体-3在骨髓增生异常综合症患者骨髓中表达呈正相关关系。结论骨髓增生异常综合症患者骨髓存在明显血管新生及血管内皮生长因子受体-3高表达,其表达水平可能参与骨髓增生异常综合症发病、发展等过程,并可能影响骨髓增生异常综合症预后,通过检测微血管密度和血管内皮生长因子受体-3的表达可为临床抗脉管新生方法治疗骨髓增生异常综合症提供实验依据。     

利用成体干细胞体外小口径血管的构建

设计了一套血管生物反应器系统,采用有限元的方法对组织工程小血管托架材料进行了分析,从而开发完成了一套用于构建直径为2 mm的小血管托架;通过收集人的原代骨髓基质干细胞(hBMSCs)和脂肪基质干细胞(ADSCs)进行体外扩增和培养,并选用第3代细胞与聚羟基乙酸酯(PGA)复合后置于血管生物反应器中动态培养;在生物反应器中动态培养4周后,对材料复合物进行取材,分别进行大体观察、HE染色和扫描电镜等指标检测.结果表明:血管色泽明亮,有一定的弹性,细胞分泌的胶原基质排列较规则,免疫组化结果表明血管含有平滑肌弹性肌动蛋白的成分.说明改进的血管生物反应器能模拟血管的力学环境,并能利用人骨髓间充质干细胞扣脂肪基质干细胞成功构建组织工程小血管组织.     

PM2.5引起的肿瘤新生血管形成和转移研究进展

 PM_2.5指直径≤2.5 μm 的颗粒物质,它很容易穿过呼吸道屏障,进入血液循环,可诱发肺癌等多种恶性肿瘤,已成为恶性肿瘤新的诱因。近年研究揭示,PM_2.5可刺激肿瘤细胞合成和分泌血管内皮生长因子（VEGF）,促进血管内皮细胞介导的肿瘤血管新生;并可激活肿瘤细胞,使其通过血管生成拟态直接形成肿瘤血管;还能使肿瘤干细胞向肿瘤内皮细胞转化,促进肿瘤新生血管形成。此外,PM_2.5可促进肿瘤细胞及其他多种细胞分泌趋化因子和白细胞介素,招募骨髓和血液中白细胞进入肿瘤组织,诱发局部慢性炎症反应,诱导上皮细胞-间充质细胞转化（EMT）的发生,增加肿瘤细胞干性、迁移和转移能力;还可破坏血管稳态,增加血管通透性,为肿瘤细胞的转移打开方便之门。PM_2.5在肿瘤的新生血管形成和转移中起了重要作用,然而,至今对其作用机制知之甚少。因此,进一步深入研究PM_2.5诱导的肿瘤新生血管形成及转移机制,能为PM_2.5引起的恶性肿瘤防治提供可靠的理论依据和新的应对策略。     

用干细胞定向培殖法修复或复制人体组织器官

近年，用血液干细胞移植的方法已攻克了血癌（白血病）。其做法是先找到ＨＬＡ（人类主要组织相容性抗原，白细胞抗原）点位与患者相同的骨髓提供者，再将其骨髓抽出来，注入经过预先摧毁原血液系统及其造血功能的患者体内，让供者骨髓内的血液干细胞在患者体内重建一套新的血液系统和造血功能。于是患者体内便流动着供髓者的血，使患者获得新生。本院已用此法治愈这类患者２０余例。 这种办法虽可治好患者的病，但别人的血毕竟基因不同，只是其ＨＬＡ在Ａ、Ｂ、ＤＲ等主要位点上相合，可接受而已，并未排除免疫反应可能，故仍存在着一定风…     

骨髓间充质干细胞体内分布及其分子机制

骨髓间充质干细胞是一类具有高度自我更新和多向分化潜能的成体干细胞，在组织修复和基因治疗上有广泛的应用前景。近来研究认为进入循环中的骨髓间充质干细胞可以迁延到广泛的组织，当组织损伤时，还可以特异性迁延到靶组织参与修复。影响骨髓间充质干细胞迁延的机制是近年研究的热点。本文就骨髓间充质干细胞体内分布及其相关分子机制的研究予以综述。     

Myocardial infarction accelerates atherosclerosis

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.     

Bone marrow cells regenerate infarcted myocardium

Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein by fluorescence-activated cell sorting on the basis of c-kit expression. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.     

Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium

Under conditions of tissue injury, myocardial replication and regeneration have been reported. A growing number of investigators have implicated adult bone marrow (BM) in this process, suggesting that marrow serves as a reservoir for cardiac precursor cells. It remains unclear which BM cell(s) can contribute to myocardium, and whether they do so by transdifferentiation or cell fusion. Here, we studied the ability of c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells to regenerate myocardium in an infarct model. Cells were isolated from transgenic mice expressing green fluorescent protein (GFP) and injected directly into ischaemic myocardium of wild-type mice. Abundant GFP+ cells were detected in the myocardium after 10 days, but by 30 days, few cells were detectable. These GFP+ cells did not express cardiac tissue-specific markers, but rather, most of them expressed the haematopoietic marker CD45 and myeloid marker Gr-1. We also studied the role of circulating cells in the repair of ischaemic myocardium using GFP+-GFP- parabiotic mice. Again, we found no evidence of myocardial regeneration from blood-borne partner-derived cells. Our data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates.     

Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts

The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.     

De novo cardiomyocytes from within the activated adult heart after injury

A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction. A therapeutic ideal--relative to cell transplantation--would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm's tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.     

Formation of haematopoietic microenvironment and haematopoietic stem cells from single human bone marrow stem cells.

Haematopoietic stem cells are a population of cells capable both of self renewal and of differentiation into a variety of haematopoietic lineages. Enrichment techniques of human haematopoietic stem cells have used the expression of CD34, present on bone marrow progenitor cells. But most CD34+ bone marrow cells are committed to their lineage, and more recent efforts have focused on the precise characterization of the pluripotent subset of CD34+ cells. Here we report the characterization of two distinct subsets of pluripotent stem cells from human fetal bone marrow, a CD34+, HLA-DR+, CD38- subset that can differentiate into all haematopoietic lineages, and a distinct more primitive subset, that is CD34+, HLA-DR-, CD38-, that can differentiate into haematopoietic precursors and stromal cells capable of supporting the differentiation of these precursors. These data represent, to our knowledge, the first identification of a single cell capable of reconstituting the haematopoietic cells and their associated bone marrow microenvironment.     

大鼠骨髓基质细胞培养的实验研究

目的探讨利用骨髓基质细胞体外培养获得神经干细胞的方法及应用.方法体外培养大鼠骨髓基质细胞;免疫组化检测;流式细胞仪检测.结果加BME的骨髓基质细胞大量分裂,形成大量的细胞分裂球,传到4代时,90%以上的细胞表达Nestin阳性.结论BME对骨髓基质细胞有明显的促分裂作用,应用此种方法可获得神经干细胞(Neural stem cell,NSC).     

脑干梗塞20例临床分析

目的：分析脑干梗塞的临床资料,探讨其中发病机制,诊断和防治方法,以及预后。方法：根据20例脑干梗塞临床资料,参阅有关文献,分析脑干梗塞发病机制,探讨其诊断方法,预后以及如何进行防治。结果：在20例脑干梗塞中,既往有高血压、动脉硬化史者11例,脑血栓5例,短暂性脑缺血2例,糖尿病2例,脑出血1例和心肌梗塞1例。结论：高血压,动脉硬化是脑干梗塞的最常见原因;病变发生的部位及进行脑CT检查的时间可能影响CT影像的真实性;脑干梗塞治愈率低,死亡率及病残率高。为此应积极治疗原发病,避免诱发因素,及时抢救,精心护理。     

骨髓间充质干细胞三维培养--构建工程组织

骨髓间充质干细胞因其可获得性、可扩增性和可多向分化性,是理想的组织工程种子细胞,用于构建工程组织。实现这一目标的主要障碍在于如何在体外模拟生理环境培养骨髓间充质干细胞,因此,研究并改进骨髓间充质干细胞体外三维培养至关重要。对近年来骨髓间充质干细胞作为组织工程种子细胞的培养方式、培养系统以及培养中的环境因素加以评述。