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1.
Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=l 7). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF Of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn I) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P＜0.05)].Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21 cm and 0.74±0.13 cm, and remarkably lower than those of the model group, which were 1.64±0.14 cm and 1.19±0.12 cm (P＜0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group,which was 53±6% (P＜0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%),the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI. 相似文献
2.
Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction 总被引：1，自引：0，他引：1
Jiang CY Gui C He AN Hu XY Chen J Jiang Y Wang JA 《Journal of Zhejiang University. Science. B》2008,9(8):630-637
Background:Bone marrow mesenehymal stem cell(MSC)transplantation is a promising strategy in the treatment of myocardial infarction(MI).However,the time for transplanting cells remains controversial.The aim of this study was to find an optimal time point for cell transplantation.Methods:MSCs were isolated and cultured from Sprague-Dawley(SD) rats.MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery.MSCs were directly injected into the infarct berder zone at 1 h,1 week and 2 weeks after MI,respectively.Sham-operated and MI centrel groups received equal volume of phosphate buffered saline(PBS).At 4 weeks after MI,cardiac function Was assessed by echocardiography;vessel density Was analyzed on hematoxylin-eosin stained slides by light microscopy;the apoptosis of cardiomyocytes Was evaluated by terminal deoxynucleotidy1 transferase-mediated dUTP nick end-labeling(TUNEL) assay;the expressions of proteins were analyzed by Western blot.Results:MSC transplantation improved cardiac function.reduced the apoptosis of cardiomyocytes and increased vessel density.These benefits were more obvious in l-week group than in 1-h and 2-week groups.There are more obvious increases in the ratio of bc1-2/bax and the expression of vascular endothelial growth factor(VEGF)and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups.Conclusion:MSC transplantation was beneficial for the recovery of cardiac function.MSC transplantation at l week post-MI exerted the best effects on increases of cardiac function,anti-apoptosis and angiogenesis. 相似文献
3.
目的:探讨外源性EGFP基因转染修饰兔骨髓间充质干细胞(m esenchymal stem cells,MSCs)的可行性。方法:用增强型荧光绿色蛋白(enhanced green fluorescent protein,EGFP)作为报告基因,以脂质体法转染骨髓间充质干细胞,观察转染结果、表达情况及对靶细胞活力的影响。结果:经荧光显微镜下观察证实:成功地对骨髓间充质干细胞实现了基因转染。结论:兔骨髓间充质干细胞能够在体外适宜的条件下进行长期培养;骨髓间充质干细胞可直接作为基因靶细胞,建立稳定表达EGFP的骨髓间充质干细胞系具有可行性,为进一步做标记的MSCs细胞的移植研究奠定基础。 相似文献
4.
Congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asym-metrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by dif-ferentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, pla-cebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction. 相似文献
5.
Cell therapy in congestive heart failure 总被引：5，自引：0，他引：5
Congestive heart failure （CHF） has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout （necrosis and apoptosis） plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells （CSCs） within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells （BMCs） to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animat CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction. 相似文献
6.
目的利用1.5T质子磁共振波谱（^1H-MRS）监测活体帕金森病大鼠模型骨髓间充质干细胞（mesenchymal stem cells,MSCs）移植治疗前后纹状体区的神经代谢变化,以探讨1．5T磁共振波谱分析在评价MSCs移植术疗效中的应用价值。方法30只正常大鼠,以6-羟基多巴胺（6-OHDA）单侧（右侧）损毁制备偏侧帕金森病模型。在活体状态下,分别于造模后3周、MSEs移植后4周及8周应用Philips1．5T临床型磁共振仪扫描,对双侧纹状体区进行^1H—MRS采集,分析该区N-乙酰天门冬氨酸／肌酸（NAA／Cr）、胆碱／肌酸（Cho／Cr）比值变化,同时对大鼠进行行为学检测。利用黑质酪氨酸羟化酶免疫组织化学染色对黑质致密部（SNc）神经元进行定量分析。结果MSCs移植后8周组（C组）大鼠损毁侧（右侧）NAA／Cr比值与未处理组（A组）和MSCs移植后4周组（B组）相比明显升高（P〈0．05）;B,C组损毁侧Cho／Cr比值较A组明显降低（P〈0．05）,且分别明显低于其对侧（P均〈0．05）。B,C组旋转圈数分别较A组低（P均〈0．05）正组旋转圈数较B组显著降低（p〈0．05）。三组损毁侧SNCTH阳性细胞生存率无显著差异（P均〉0．05）。结论1．5T磁共振波谱可以作为一种活体无创性检测方法,对帕金森病大鼠模型纹状体区MSCs细胞移植疗效进行动态监测而作出有价值的评价。 相似文献
7.
XIA Qin-gui *L Oliver Chung Heidi Spitznagel Thomas Unger 《Journal of Zhejiang University. Science. B》2001,(4)
ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅＮａ /Ｈ ｅｘｃｈａｎｇｅｒ (ＮＨＥ)ｉｓａｐＨ ｒｅｇｕｌａｔｏｒｙｐｒｏｔｅｉｎｐｒｅｓｅｎｔｉｎｔｈｅｐｌａｓｍａｍｅｍ ｂｒａｎｃｅｏｆｃａｒｄｉｏｍｙｏｃｙｔｅｓａｎｄｏｔｈｅｒｃｅｌｌｔｙｐｅｓ.ＡｌｔｈｏｕｇｈｓｅｖｅｒａｌｉｓｏｆｏｒｍｓｏｆＮＨＥｈａｖｅｂｅｅｎｄｅ ｃｒｉｂｅｄ,ｔｈｅｐｒｅｄｏｍｉｎａｎｔｉｓｏｆｏｒｍｉｎｔｈｅｈｅａｒｔｉｓｔｈｅｕｂｉｑｕｉｔｏｕｓＮＨＥ 1 ,ｗｈｉｃｈｕｎｄｅｒｃｅｎｔａｉｎｐｈｙｓｉｏｌｏｇｉｃａｌｃｏｎｄｉｔｉ… 相似文献
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9.
Jin-jing Wang Feng Ye Li-jia Cheng Yu-jun Shi Ji Bao Huai-qiang Sun Wei Wang Peng Zhang Hong Bu 《Journal of Zhejiang University. Science. B》2009,10(5):355-367
Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialo-protein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering. 相似文献
10.
11.
Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells 总被引：3，自引：0，他引：3
Xiang Y Zheng Q Jia BB Huang GP Xu YL Wang JF Pan ZJ 《Journal of Zhejiang University. Science. B》2007,8(2):136-146
This study is aimed at investigating the potentials of ex vivo expansion and pluri-differentiation of cryopreservation of adult human bone marrow mesenchymal stem cells （hMSCs） into chondrocytes, adipocytes and neurocytes. Cryopreserved hMSCs were resuscitated and cultured for 15 passages, and then induced into chondrocytes, adipocytes and neurocytes with corresponding induction medium. The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin. The result showed that the resuscitated cells could differentiate into chondrocytes after exposure to transforming growth factor 61 （TGF-~0, insulin-like growth factor I （IGF-I） and vitamin C （Vc）, and uniformly changed morphologically from a spindle-like fibroblastic appearance to a polygonal shape in three weeks. The induced cells were heterochromatic to safranin O and expressed cartilage matrix-procollagenal （If） mRNA. The resuscitated cells cultured in induction medium consisting of dexamethasone, 3-isobutyl-l-methylxanthine, indomethacin and IGF-I showed adipogenesis, and lipid vacuoles accumulation was detectable after 21 d. The resuscitated hMSCs were also induced into neurocytes and expressed nestin and neuron specific endolase （NSE） that were special surface markers associated with neural cells at different stage. This study suggested that the resuscitated hMSCs should be still a population ofpluripotential cells and that it could be used for establishing an abundant bMSC reservoir for further experiment and treatment of various clinical discases. 相似文献
12.
Mei-xiang Xiang Ai-na He Jian-an Wang Chun Gui 《Journal of Zhejiang University. Science. B》2009,10(8):619-624
Objective The aim of this study was to test the protective effect of mesenchymal stem cells (MSCs) on cardiomyocytes in vitro and to
investigate the anti-apoptotic signaling pathway.
Methods MSCs from Sprague-Dawley (SD) rats were separated and cultured. MSC medium was collected from MSCs cultured in serum-free
Dulbecco’s modified eagle medium (DMEM) under hypoxia. Cultured cardiomyocytes from neonatal SD rats were exposed to hypoxia/reoxygenation
(H/R) and treated with MSC medium. The apoptotic cardiomyocytes were stained with Annexin-V-fluorescein isothiocyanate (FITC),
Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The mitochondrial transmembrane
potential of cardiomyocytes was assessed using a fluorescence microscope. The expression of Bcl-2, Bax, cytochrome C, apoptosis-induced
factor (AIF), and caspase-3 was tested by Western blot analysis.
Results Our data demonstrated that MSC medium reduced H/R-induced cardiomyocyte apoptosis, increased the Bcl-2/Bax ratio, and reduced
the release of cytochrome C and AIF from mitochondria into the cytosol.
Conclusion MSCs protected the cardiomyocytes from H/R-induced apoptosis through a mitochondrial pathway in a paracrine manner.
Project supported by the National Natural Science Foundation of China (No. 30670868) and the Natural Science Foundation of
Zhejiang Province, China (No. R206007) 相似文献
13.
Objective: In addition to pH regulation, Na+/H+ exchange (NHE) has been shown to facilitate cell growth and proliferation. However, the effects of long-term inhibition of
Na+/H+ exchange on cardiac structural and functional remodeling post myocardial infarction (MI) are still controversial. The present
study was therefore carried out to further investigate the effects of long-term treatment with cariporide, a specific inhibitor
of NHE-1, on cardiac remodeling after MI in rats; Methods: Male Wistar rats that underwent coronary ligation were randomly
selected for cariporide treatment starting 6 h after induction of MI or no treatment. Treatment was continued up to 6 weeks
post MI, after which, the arterial, venous and left ventricular catheters were chronically implanted. Twenty-four h later,
after hemodynamic signals were recorded in conscious rats, they were sacrificed and hearts were taken out for morphological
examinations; Results: Cariporide treatment decreased the heart weight and heart weight to body weight ratio (bothP<0.05), decreased left ventricular end-diastolic pressure (P<0.001), improved myocardial contractility (dP/dt
max) (P<0.05) and tended to increase the survival of treated rats compared to that of untreated infarct rats; Conclusion: The results
of the present study indicate that the long-term inhibition of NHE with cariporide can attenuate cardiac structural remodeling
and improve left ventricular dysfunction in infarcted rats, and suggest that Na+/H+ exchange inhibition could be an effective therapeutic strategy for myocardial infarction-induced heart failure. 相似文献
14.
Ze-wei Tao Long-gui Li Zhao-hua Geng Tao Dang Shan-jun Zhu 《Journal of Zhejiang University. Science. B》2010,11(4):238-248
Therapeutically delivered mesenchymal stem cells (MSCs) improve ventricular remodeling. However,the mechanism underlying MSC cardiac remodeling has not been clearly determined. Congestive heart failure (CHF) was induced in rats by cauterization of the left ventricular free wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 d after injury. Ten weeks later,when compared with sham operation,CHF significantly increased nucleus mitotic index,capilla... 相似文献
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INTRODUCTION Pulmonary hypertension is not rare in humanwith some heart and lung diseases. Chronic pul-monary hypertension leads to structural alterationsof the lung vessels. The pathophysiology of thisremodeling process is still poorly understood.Furthermore, the structural damage of the lungvessels limits the clinical success of vasodilatortreatment. Assuming genetic susceptibility, shearstress and inflammation are the principal pathoge-netic factors involved in lung vessel remode… 相似文献
16.
Jun-xian CAO Lu FU Qian-ping GAO Rong-sheng XIE Fan QU 《Journal of Zhejiang University. Science. B》2014,15(6):515-521
Objective
To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin (SM) on these changes in vivo.Methods
Sixty Wistar rats were divided randomly into four groups: a control group (n=15), an SM group (n=15), a myocardial infarction (MI) group (n=15), and an MI+SM group (n=15). Chronic MI was obtained by ligating the left anterior descending branch (LAD) of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels (SACs) was achieved by intramuscular injection of SM (180 mg/(kg·d)) for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential (MAP). The effect of stretching was examined by assessing the 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVBs), and ventricular tachycardia (VT).Results
The MAPD90 decreased during stretching in both the control (from (50.27±5.61) ms to (46.27±4.51) ms, P<0.05) and MI groups (from (65.47±6.38) ms to (57.47±5.76 ms), P<0.01). SM inhibited the decrease in MAPD90 during inflation ((46.27±4.51) ms vs. (49.53±3.52) ms, P<0.05 in normal hearts; (57.47±5.76) ms vs. (61.87±5.33) ms, P<0.05 in MI hearts). The occurrence of PVBs and VT in the MI group increased compared with that in the control group (PVB: 7.93±1.66 vs. 1.80±0.86, P<0.01; VT: 7 vs. 1, P<0.05). SM decreased the occurrence of PVBs in both normal and MI hearts (0.93±0.59 vs. 1.80±0.86 in normal hearts, P<0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P<0.01).Conclusions
Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback (MEF), but that there might be other mechanisms involved in causing VT in chronic MI. 相似文献17.
目的：观察奥扎格雷钠与黄芪注射液联合治疗糖尿病肾病的疗效。方法：将84例早期糖尿病肾病患者随机分为3组，每组28例，在常规治疗的基础上，A组加用黄芪注射液，B组加用奥扎格雷钠注射液，C组加用黄芪注射液与奥扎格雷钠注射液，疗程均为20d。观察治疗前后各组尿白蛋白排泄率（UAER），血尿素氮（BUN），血清肌酐（SCr），糖化血红蛋白（HbAlc）的变化。结果：糖化血红蛋白，血清肌酐，血尿素氮，尿白蛋白排泄取：3组治疗后均比治疗前显著下降（P〈0．01），C组下降幅度优于A组和B组（P〈0．05）。结论：奥扎格雷钠联合黄芪注射液治疗糖尿病肾病能降低糖化血红蛋白，显著降低尿白蛋白排泄率，同时改善肾功能。 相似文献
18.
Effect of matrine and carvedilol on collagen and MMPs activity of hypertrophy myocardium induced by pressure overload 总被引：3，自引：0，他引：3
Zhang YJ Xiang MX San J Cheng G Wang SS 《Journal of Zhejiang University. Science. B》2006,7(3):245-250
INTRODUCTION Matrine, a monomer of traditional Chinese medi-cine, comes from leguminosae plants such as Kusheng, is quinoilizidine with four-loop and molecular formula of C15H24N20. Matrine has been proved to have anti-arrhythmia (Xu et al., 2004), anti-hypoxia and decreasing heart rate effects (Zhang et al., 1990a; 1990b) in many animal experiments, and has the role of inducing calmness (Luo et al., 2001) and lowering body temperature (Tao and Wan, 1992). Traditional Chinese medicin… 相似文献
19.
Dan-li Fu Qiao-hong Jiang Fu-ming He Guo-li Yang Li Liu 《Journal of Zhejiang University. Science. B》2012,13(5):364-371
The purpose of this study was to analyze the effect of strontium-substituted hydroxyapatite (Sr-HA) on bone osseointegration
of the implants using fluorescence microscopy. We allocated 20 implants to two groups: Sr-HA group and HA group. Electrochemically
deposited HA and Sr-HA coatings were applied onto the implants separately. All the implants were inserted into femur bone
of rabbits. Oxytetracycline hydrochloride, alizarin-complexon, and calcein green were respectively administered 7, 28, and
46 d after the implantation. After eight weeks, femurs were retrieved and prepared for the fluorescence microscopy observation.
We analyzed the bone mineral apposition rates (MARs), bone area ratios (BARs), and bone to implant contact (BIC) of the two
groups. Fluorescence microscopic observation showed that all groups exhibited extensive early peri-implant bone formation.
The MAR of the Sr-HA group was greater than that for pure HA from 7 to 28 d after implantation, but no significant difference
was found at later stage. And the BIC showed difference at 7 and 28 d compared with pure HA. We concluded that Sr-HA coating
can improve the bone osseointegration of the implant in the early stage compared with the HA coating. 相似文献
20.
Xian-bao Liu Han Chen Hui-qiang Chen Mei-fei Zhu Xin-yang Hu Ya-ping Wang Zhi Jiang Yin-chuan Xu Mei-xiang Xiang Jian-an Wang 《Journal of Zhejiang University. Science. B》2012,13(8):616-623