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1.
    
Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non‐ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1–4 days after left anterior descending coronary artery (LAD)‐ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium.  相似文献   

2.
    
The midterm effects of cardiac telocytes (CTs) transplantation on myocardial infarction (MI) and the cellular mechanisms involved in the beneficial effects of CTs transplantation are not understood. In the present study, we have revealed that transplantation of CTs was able to significantly decrease the infarct size and improved cardiac function 14 weeks after MI. It has established that CT transplantation exerted a protective effect on the myocardium and this was maintained for at least 14 weeks. The cellular mechanism behind this beneficial effect on MI was partially attributed to increased cardiac angiogenesis, improved reconstruction of the CT network and decreased myocardial fibrosis. These combined effects decreased the infarct size, improved the reconstruction of the LV and enhanced myocardial function in MI. Our findings suggest that CTs could be considered as a potential cell source for therapeutic use to improve cardiac repair and function following MI, used either alone or in tandem with stem cells.  相似文献   

3.
    
Telocytes (TCs) are a novel type of interstitial cells only recently described. This study aimed at characterizing and quantifying TCs and telopodes (Tps) in normal and diseased hearts. We have been suggested that TCs are influenced by the extracellular matrix (ECM) composition. We used transmission electron microscopy and c-kit immunolabelling to identify and quantify TCs in explanted human hearts with heart failure (HF) because of dilated, ischemic or inflammatory cardiomyopathy. LV myectomy samples from patients with aortic stenosis with preserved ejection fraction and samples from donor hearts which could not be used for transplantation served as controls. Quantitative immunoconfocal analysis revealed that 1 mm2 of the normal myocardium contains 14.9 ± 3.4 TCs and 41.6 ± 5.9 Tps. As compared with the control group, the number of TCs and Tps in HF decreased more than twofold. There were no differences between HF and control in the number of Ki67-positive TCs. In contrast, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive TCs increased threefold in diseased hearts as compared to control. Significant inverse correlations were found between the amount of mature fibrillar collagen type I and the number of TCs (r = −0.84; P < 0.01) and Tps (r = −0.85; P < 0.01). The levels of degraded collagens showed a significant positive relationship with the TCs numbers. It is concluded that in HF the number of TCs are decreased because of higher rates of TCs apoptosis. Moreover, our results indicate that a close relationship exists between TCs and the ECM protein composition such that the number of TCs and Tps correlates negatively with the amount of mature fibrillar collagens and correlates positively with degraded collagens.  相似文献   

4.
目的:建立基于显微形态标记及流式分选分离大鼠心脏Telocytes(CTs)的方法。方法:采用抗体c-Kit免疫磁珠法获得原代心脏Telocytes,显微注射Di I标记具\"Telopode\"典型形态的细胞,使用流式分离及回收单个Di I+细胞;使用免疫荧光技术和RT-PCR方法对经回收的单个细胞来源的细胞进行表型鉴定。结果:显微注射Di I能较好地标记具Telocytes典型形态的细胞,结合流式分选及单细胞回收,能有效回收经标记的Di I+细胞,经回收的Di I标记阳性Telocytes的贴壁率为14.9%,增殖率为5.6%,呈克隆样生长率为2.4%,该呈克隆样生长的细胞能通过消化传代。免疫荧光染色证明,该回收Telocytes表达其相对特异性表面标记物c-Kit和CD34,RT-PCR的结果也证明:经回收Telocytes表达其相对特异基因c-Kit、CD34、Vimentin和PDGFR-β。结论:研究所建立的方法能有效分离及单细胞回收高纯度的心脏Telocytes,经回收的心脏Telocytes具有增殖及传代能力,且能维持其特异表型。  相似文献   

5.
    
Cardiovascular diseases are the number one cause of death globally and are projected to remain the single leading cause of death. Treatment options abounds, although efficacy is limited. Recent studies attribute discrete and ephemeral benefits to adult stem cell therapies, indicating the urge to improve stem cell based–therapy. In this study, we show that priming mesenchymal stem cells (MSC) towards cardiomyogenic lineage enhances their beneficial effects in vivo as treatment option for acute phase myocardial infarction. MSC were primed using cardiomyogenic media for 4 days, after which peak expression of key cardiomyogenic genes are reached and protein expression of Cx‐43 and sarcomeric α‐actinin are observed. MSC and primed MSC (pMSC) were characterized in vitro and used to treat infarcted rats immediately after left anterior descending (LAD) occlusion. Echocardiography analysis indicated that MSC‐treated myocardium presented discrete improvement in function, but it also showed that pMSC treatment lead to superior beneficial results, compared with undifferentiated MSC. Seven days after cell injection, MSC and pMSC could still be detected in the myocardium. Connexin‐43 expression was quantified through immunoblotting, and was superior in pMSC, indicating that this could be a possible explanation for the superior performance of pMSC therapy.  相似文献   

6.
    
Evidence has been given that the adult heart contains a specific population of stromal cells lying in close spatial relationship with cardiomyocytes and with cardiac stem cells in sub‐epicardial cardiogenic niches. Recently termed ‘telocytes’ because of their long cytoplasmic processes embracing the parenchymal cells, these cells have been postulated to be involved in heart morphogenesis. In our opinion, investigating the occurrence and morphology of telocytes during heart histogenesis may shed further light on this issue. Our findings show that typical telocytes are present in the mouse heart by early embryonic to adult life. These cells closely embrace the growing cardiomyocytes with their long, slender cytoplasmic processes. Hence, in the developing myocardium, telocytes may play nursing and guiding roles for myocardial precursors to form the correct three‐dimensional tissue architectural pattern, as previously suggested.  相似文献   

7.
    
Cell-based therapy is considered a novel and potentially new strategy in regenerative medicine. But the efficacy of cell-based therapy has been limited by the poor survival of the transplanted cells in an ischaemic environment. The goal of the present study is to present a possibility to increase survival of the transplanted cardiomyocytes, by increasing the vascularization of the infarcted area. First, we injected endothelial progenitor cells (EPCs) to augment the vascular density in infarcted areas and to improve the benefit of a subsequent Tx of foetal cardiomyocytes. Serial echocardiography indeed showed significant improvement of the left ventricular function after application of EPC and a significant additive improvement after Tx of foetal cardiomyocytes. In contrast, repetitive EPC transplantation as a control group did not show an additional improvement after the second transplantation. Histologically, cells could be readily detected after Tx by BrdU-staining for EPC and by carboxy-fluorescein diacetate succinimidyl ester (CFSE)-staining for foetal cardiomyocytes. Staining for CD31 revealed a significant increase in vessel density in the infarction area compared with medium controls, possibly contributing to the benefit of transplanted foetal cardiomyocytes. Notably, a significant increase in the number of apoptotic cells was observed in cell-transplanted hearts accompanied by an increase in proliferation, collagen content and neutrophil infiltration, suggesting an active remodelling concomitant with sustained inflammatory processes. In conclusion, repetitive Tx of different cell types after myocardial infarction in rat hearts significantly improved left ventricular function and could represent a feasible option to enhance the benefit of cell therapy.  相似文献   

8.
Summary Both cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.  相似文献   

9.
    
Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Until recently, it was thought that myocardium was not able to repair itself, but studies have now shown that resident cardiac stem cells have regenerative capacity, and stem cell therapy may be a novel approach for cardiac muscle repair and regeneration. Stem cell-derived paracrine factors have been shown to regulate ventricular remodeling, inflammation, apoptosis, cardiomyocytes regeneration, and neovascularization in regions of infarcted cardiac tissue. In this review, we summarize the evidence from cellular, animal, and clinical studies supporting the potential clinical significance of stem cell therapy as a novel therapeutic approach for the treatment of MI.  相似文献   

10.
11.
心室的舒张性能和顺应性是心脏功能的两个重要方面。为了查明心肌梗塞后这两个特性的演变规律,我们在离体条件下观察了大鼠心脏舒张性能和顺应性在左冠状动脉结扎后2秒到21天之间的动态过程。实验表明,结扎冠状动脉后,左室舒张性能指标有明显改变(T值延长,-dp/dtmax降低),在恢复期未见明显改善;左室顺应性的变化有明显的时相性,表现为先有一过性增高,之后明显降低,继而回升到接近对照水平,到恢复期则明显增高。  相似文献   

12.
    
Thus far, the cellular and molecular mechanisms related to early (especially within 24 hours after acute myocardial infarct (MI)) exercise‐mediated beneficial effects on MI have not yet been thoroughly established. In the present study, we demonstrated that acute MI rats that underwent early moderate exercise training beginning one day after MI showed no increase in mortality and displayed significant improvements in MI healing and ventricular remodelling, including an improvement in cardiac function, a decrease in infarct size, cardiomyocyte apoptosis, cardiac fibrosis and cardiomyocyte hypertrophy, and an increase in myocardial angiogenesis, left ventricular wall thickness and the number of cardiac telocytes in the border zone. Integrated miRNA‐mRNA profiling analysis performed by the ingenuity pathway analysis system revealed that the inhibition of the TGFB1 regulatory network, activation of leucocytes and migration of leucocytes into the infarct zone comprise the molecular mechanism underlying early moderate exercise‐mediated improvements in cardiac fibrosis and the pathological inflammatory response. The findings of the present study demonstrate that early moderate exercise training beginning one day after MI is safe and leads to significantly enhanced MI healing and ventricular remodelling. Understanding the mechanism behind the positive effects of this early training protocol will help us to further tailor suitable cardiac rehabilitation programmes for humans.  相似文献   

13.
再生医学是一门研究如何促进创伤与组织再生及功能重建的新兴学科,主要通过研究干细胞分化、机体等正常组织创伤修复与再生等机制来维持、修复、再生或改善损伤组织和器官功能。脂肪干细胞(adipose-derived stem cells,ASCs)是近年来从脂肪组织中分离得到的一种具有多向分化潜能的干细胞,是一种足量的、可用于实际的、有一定吸引力的自体细胞代替的供体资源,并能够广泛的用于组织修复、再生、发育的可塑性及细胞治疗等研究中。阐述了脂肪干细胞在旁分泌、软组织重建及损伤修复、骨骼肌重建、心血管重建、神经系统重建及癌症转移与入侵方面的作用模式,概括总结了目前利用脂肪干细胞参与的临床治疗方法,以期对脂肪干细胞在再生医学中应用研究提供参考。  相似文献   

14.
    
In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation.  相似文献   

15.
16.
The existence of a new type of interstitial cells in the heart namely, interstitial Cajal-like cells (ICLC), has been described for the first time by Hinescu and Popescu in 2005. This study was then followed by an ascending trend of publications regarding the morphology, phenotype and distribution of myocardial ICLC in diverse species including human patients. Recently the new term ‘telocytes’ has been proposed for cells formerly known as ICLC, and the term ‘telopodes’ has been proposed for the prolongations of these cells. The identification of these cells is based on ultrastructural criteria. In addition, telocyters/telyopodes can be identified by several complementary approaches including methylene blue vital staining, silver impregnation and immunoreactivity against CD117/c-kit, vimentin, etc. This point of view presents critical data existing in literature, as well as own results, which unequivocally provide compelling evidence that telocytes are a new distinct cellular entity of myocardial interstitium. Several presumable functions of the myocardial telocytes are discussed: (i) intercellular signalling, (ii) cardiac repair/remodelling and (iii) stem cell nursing in cardiac renewal.  相似文献   

17.
    
Recent evidence indicates that the adult heart contains sub-epicardial cardiogenic niches where cardiac stem cells and stromal supporting cells reside together. Such stromal cells include a special population, previously identified as interstitial Cajal-like cells and recently termed telocytes because of their long, slender processes (telopodes) embracing the myocardial precursors. Specific stromal cells, presumptively originated from the epicardium, have been postulated to populate the developing heart where they are thought to play a role in its morphogenesis. This study is designed to investigate the occurrence of telocytes in the developing heart and provide clues to better understand their role as supporting cells involved in the architectural organization of the myocardium during heart development. Our results showed that stromal cells with the immunophenotypical (vimentin, CD34) and ultrastructural features of telocytes were present in the mouse heart since early embryonic to adult life, as well as in primary cultures of neonatal mouse cardiac cells. These cells formed an extended network of telopodes which closely embraced the growing cardiomyocytes and appeared to contribute to the aggregation of cardiomyocyte clusters in vitro. In conclusion, the present findings strongly suggest that, during heart development, stromal cells identifiable as telocytes could play a nursing and guiding role for myocardial precursors to form the correct three-dimensional tissue pattern and contribute to compaction of the embryonic myocardial trabeculae. It is tempting to speculate that telocytes could be a novel, possible target for therapeutic strategies aimed at potentiating cardiac repair and regeneration after ischemic injury.  相似文献   

18.
    
The effects of cyclical expansion and elaxation of the vessel wall on endothelial cell metabolism have been modeled using a uniaxial strain device and cultured endothelial cell monolayers. Also, the effects of stopping and then restarting cyclic strain on metabolite secreation rates were determined. Secretion rates of prostacyclin (PGI(2)), endothelin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-type 1 (PaI-1) by endothelial cells were constant over24-h periods The secreation of both PGI(2) and endothelin was enhanced in cells exposed to high physiological levels of cyclical strain (10% at 1Hz) compared with controls, while tPA production was unaltered. These results were true for both human and bovine endothelial cells. Characterization of the response of human endothelial cells to cyclical strain made evaluation of stretch effects on PAl-1 secretion possible. A nearly twofold increase in PAl-1 secretion by cells exposed to arterial levels of strain was observed. Endothelin secretion remained elevated even after strain was stopped for 12 h, while PGl(2) secretion returned to control values upon cessation of cyclic stretch. These results indicate that physiological levels of cyclic mechanical strain ca significantly modulate secretion of vasoactive metabolited form endothelial cells. The changes sen secretion are, in some cases, quite different from those caused by arterial levels of fluid shear stress exposure. (c) 1994 John Wiley & Sons, Inc.  相似文献   

19.
    
Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration. Human villous trophoblasts (HVTs) play key roles in embryonic implantation and placentation. In this study, we show that HVTs can promote tube formation of human umbilical vein endothelial cells (HUVECs) on Matrigel and enhance the resistance of neonatal rat cardiomyocytes (NRCMs) to oxidative stress in vitro. Delivery of HVTs to ischaemic area of heart preserved cardiac function and reduced fibrosis in a mouse model of acute myocardial infarction (AMI). Histological analysis revealed that transplantation of HVTs promoted angiogenesis in AMI mouse hearts. In addition, our data indicate that HVTs exert their therapeutic benefit through paracrine mechanisms. Meanwhile, injection of HVTs to mouse hearts did not elicit severe immune response. Taken together, our study demonstrates HVT may be used as a source for cell therapy or a tool to study cell‐derived soluble factors for AMI treatment.  相似文献   

20.
Determining which time point is optimal for bone marrow-derived cell (BMC) transplantation for acute myocardial infarction (AMI) has attracted a great deal of attention. Studies have verified the interaction between cell treatment effect and transfer timing and have suggested that the optimal time frame for BMC therapy is day 4 to day 7 after AMI. However, the potential mechanism underlying the time-dependent therapeutic response remains unclear. Recently, a growing body of in vitro evidence has suggested that stem cells are able to feel and respond to the stiffness of their microenvironment to commit to a relevant lineage, indicating that soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Simultaneously, considering the fact that the myocardium post-infarction experiences a time-dependent stiffness change from flexible to rigid as a result of myocardial remodelling following tissue necrosis and massive extracellular matrix deposition, we presume that the myocardial stiffness within a certain time frame (possibly day 4–7) post-AMI might provide a more favourable physical microenvironment for the phenotypic plasticity and functional specification of engrafted BMCs committed to some cell lineages, such as endothelial cells, vascular smooth muscle cells or cardiomyocytes. The beneficial effect facilitates angiogenesis and myocardiogenesis in the infarcted heart, and subsequently leads to more amelioration of cardiac functions. If the present hypothesis were true, it would be of great help to understand the mechanism underlying the optimal timing for BMC transplantation and to establish a direction for the time selection of cell therapy.  相似文献   

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