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目的 研究肝细胞生长因子及其受体在骨髓干细胞移植治疗中的表达情况 ,评价其作用。方法 大鼠 30只 ,其中 15只接受了冠状动脉前降支结扎以引起前壁心肌梗死 ,另外 15只同时还进行了骨髓单个核细胞心肌移植。术后不同时间点心脏取材检测肝细胞生长因子及其受体的表达。结果 心肌梗死之后心肌组织肝细胞生长因子及其受体表达水平增加 ;同时接受骨髓单个核细胞心肌移植治疗没有进一步增加肝细胞生长因子的表达 ,但其受体的表达水平进一步显著增加 (P <0 0 1)。结论 骨髓单个核细胞心肌移植治疗能够增加肝细胞生长因子受体的表达水平。 相似文献
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目的研究内皮祖细胞(EPC)移植治疗糖尿病兔下肢缺血对血管生成相关基因表达的影响。方法日本大耳白兔16只,四氧嘧啶法建立糖尿病模型后,随机分为磷酸盐缓冲液(PBS)对照组与EPC治疗组,分别用PBS和骨髓来源经体外扩增的EPC移植于下肢缺血区,14天后用基因芯片分析EPC移植对血管生成相关基因表达的影响,同时检测肌浆中血管内皮生长因子(VEGF)浓度。结果EPC治疗组下肢缺血区27个血管生成基因表达上调超过2倍,移植治疗组VEGF的浓度显著高于对照组,差异有统计学意义。结论EPC植入糖尿病兔下肢缺血区,可以上调包括VEGF在内的多种血管生成相关基因,同时肌浆中VEGF水平升高。 相似文献
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运用基因芯片初步研究类风湿关节炎患者外周血单个核细胞基因表达谱特征 总被引:1,自引:0,他引:1
目的运用基因芯片技术研究类风湿关节炎(RA)基因表达谱特征,从全基因组角度探讨RA相关致病基因。方法提取5例活动期RA患者和3名健康对照者外周血单个核细胞(PBMC)中总RNA,Illumina寡核苷酸基因芯片分析每个样本的48 000个基因变化。反转录-聚合酶链反应(RT-PCR)验证芯片结果。结果RA患者与健康对照者相比2倍上调基因122个,2倍下调基因29个。分子及生物功能分析显示上调表达的基因涉及传递蛋白、蛋白翻译合成、代谢、转录调控、信号转导、趋化因子、细胞周期和凋亡相关基因等种类。结论RA涉及多环节的病理过程,基因芯片技术有利于进一步揭示RA分子机制,发现新的治疗靶标。 相似文献
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经冠脉移植骨髓单个核细胞和间充质干细胞治疗急性心肌梗死的对比实验研究 总被引:2,自引:1,他引:2
目的 对比研究经冠脉骨髓单个核细胞(BM-MNC)和间充质干细胞(MSC)移植对实验性急性心肌梗死(AMI)心功能的影响及其机制.方法 选用12只雄性冀中白猪随机分为:正常对照组、AMI模型组、BM-MNC组、MSC组各3只,经导管球囊封闭前降支制作AMI的动物模型,于梗死后1 h直接冠脉球囊成型术后经OTW球囊注入骨髓干细胞.分别于术前及术后4 w经心脏超声检测心功能,4 w后取材行光、电镜病理学检查,实时定量RT-PCR检测心肌血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)mRNA表达.结果 4 w时干细胞组比AMI模型组室壁运动异常指数显著减轻(P<0.05)、射血分数显著提高(P<0.01).与AMI模型组相比:BM-M;NC和MSC组梗死区及梗死边缘区血管数显著增多、BM-MNC组增加比MSC组显著(P<0.01),心肌细胞凋亡指数显著降低,BM-MNC组及MSC组间无明显差异(P<0.01).干细胞移植组梗死边缘区冠脉血管周围可见异常细胞生长,有毛细血管"芽生"现象,可见不成熟的心肌细胞和细胞凋亡.4 w时左室射血分数(LVEF)与心肌血管数成正相关(r=0.694 9,P=0.037 7),LVEF与心肌细胞凋亡指数成负相关(r=0.913 3,P=0.000 6).BM-MNC组,心肌梗死区及梗死边缘区VEGF基因表达比其他三组均明显增加(梗死区F=4.23,P=0.045 6,边缘区F=5.66,P=0.022 3).BM-MNC及MSC组心肌梗死区bFGF基因表达比梗死模型组显著增加(梗死区F=7.49,P=0.010 4).结论 经冠脉骨髓单个核细胞和间充质干细胞移植均可改善实验性AMI心功能;改善心功能的机理与梗死区及梗死边缘区VEGF及bFGF表达增加,血管密度增加,心肌细胞凋亡减少有关;骨髓单个核细胞移植的促血管增生作用优于间充质干细胞移植. 相似文献
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目的应用寡核苷酸基因芯片技术建立家族不良结局乙型肝炎病毒(HBV)感染者外周血单个核细胞的基因表达谱。方法在一个家族不良结局HBV感染家族中,选取患者5例,患者正常配偶4 例,提取外周血单个核细胞RNA,与涵盖2.2万个ESTs的寡核苷酸表达谱基因芯片U133A 2.0杂交,通过Affymetrix扫描仪和DNT分析软件比较患病组与对照组外周血单个核细胞基因表达谱,获得基因的相对表达比值。结果在2.2万个ESTs中初筛出55个差异表达基因,表达上调14个,表达下调41个,差异基因主要(57%)参与免疫反应、细胞信号转导、细胞周期、代谢、细胞凋亡及炎症基因。结论筛选出的55个基因,是宿主感染HBV的差异表达基因,或宿主对HBV的易感基因,为差异表达基因功能研究建立框架,为宿主HBV易感性研究提供新的靶点。 相似文献
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纯化人源骨髓单克隆间充质细胞移植更利于梗死心脏功能恢复 总被引:7,自引:0,他引:7
目的通过制备大鼠心肌梗死模型,分别移植经纯化了的人源骨髓单克隆间充质干细胞(SCMSCs)、未纯化的间充质细胞和单个核细胞及外周血单个核细胞,旨在比较SCMSCs移植是否更有利于心脏功能改善。方法应用磁珠分选和极限稀释细胞培养方法获取SCMSCs,利用贴壁培养方法得到未纯化的骨髓间充质细胞,利用梯度密度离心法得到骨髓单个核细胞和外周血单个核细胞。流式细胞仪分析所得细胞特性后,将其移植到梗死心脏。术后1个月,应用血流动力学技术检测大鼠心脏功能,随后取材,以免疫荧光检测移植细胞的分化情况,用碱性磷酸法计算血管密度。结果流式分析结果显示,SCMSCs99%以上表达间充质干细胞标记蛋白,阴性表达造血细胞标记蛋白。功能检测显示,移植SCMSCs心脏收缩功能(LVdP/dtmax)较明显高于其他各组。血管计数显示,SCMSC组血管密度明显高于其他各组。免疫荧光结果显示,移植的SCMSCs向心肌细胞和血管内皮细胞转化效率明显高于其他骨髓细胞,外周血细胞并不发现分化。结论经纯化均一的SCMSCs移植较目前常用的未纯化、不均一的干细胞移植更利于梗死心脏收缩功能恢复。 相似文献
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甲状旁腺素相关肽对骨髓基质细胞中RANKL及OPG基因的表达影响 总被引:2,自引:0,他引:2
目的 研究甲状旁腺素相关肽(PTHrP)对骨髓基质细胞RANKL/OPG基因表达的影响。方法 分离小鼠骨髓细胞后,45ng/ml的PTHrP刺激,第6天时观察破骨细胞生成情况。90ng/mlPTHrP刺激贴壁鼠骨髓基质细胞3d和6d,实时荧光PCR检测破骨细胞分化因子RANKL及骨保护素OPG基因的表达情况。结果在PTHrP的刺激下,大量破骨细胞生成。骨髓基质细胞在PTHrP的刺激下,RANKI基因表达升高,OPG基因表达降低。结论 PTHrP刺激破骨细胞生成是通过上调RANKI基因表达,下调OPG基因的表达实现的。 相似文献
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目的 应用基因芯片技术分析原发性胆汁性肝硬化患者外周血单个核细胞的基因表达谱特征.方法 选取9例原发性胆汁性肝硬化患者、9名健康对照为研究对象,提取其外周血单个核细胞总RNA,进行人类全基因组寡核苷酸芯片(约22000个基因)检测,筛选出差异表达基因及相关信号通路.结果 原发性胆汁性肝硬化患者外周血单个核细胞中差异表达的基因共有79个,其中21个表达上调,58个表达下调.这些基因对应着27条信号通路,其中有6条通路参与了免疫调控及细胞凋亡过程,分别是自然杀伤细胞介导的细胞毒通路、Toll样受体信号通路、抗原加工提呈通路、细胞因子相互作用通路、T细胞受体信号通路、细胞凋亡通路.结论 原发性胆汁性肝硬化患者外周血单个核细胞中存在特有的差异表达基因,针对这些基因及相关信号通路的进一步研究,将为探索发病机制和寻找生物标志物提供新的方向. 相似文献
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转染人血管内皮生长因子165基因的骨髓间充质干细胞移植改善兔心肌梗死后心功能 总被引:1,自引:0,他引:1
目的探讨将骨髓间充质干细胞移植和血管内皮生长因子基因治疗相结合治疗兔心肌梗死的疗效及其机制。方法将48只新西兰大白兔随机分为心肌梗死组、骨髓间充质干细胞移植组、血管内皮生长因子组和骨髓间充质干细胞 血管内皮生长因子组。建立兔心肌梗死模型,在心肌梗死后2周取107个骨髓间充质干细胞移植至梗死区。移植后4周测定心功能,梗死区骨髓间充质干细胞进行鉴定及计数,进行Ⅷ因子免疫组织化学染色。结果血流动力学比较发现,骨髓间充质干细胞 血管内皮生长因子组各项参数明显优于骨髓间充质干细胞组;心肌梗死区BrdU阳性细胞数骨髓间充质干细胞 血管内皮生长因子组明显多于骨髓间充质干细胞组(61.24±8.51个/视野比44.21±7.68个/视野,P<0.01);梗死区血管的数量骨髓间充质干细胞 血管内皮生长因子组(48.75±7.96个/视野)明显多于骨髓间充质干细胞组(33.08±6.12个/视野,P<0.01)、血管内皮生长因子组(29.98±8.04个/视野,P<0.01)和心肌梗死组(18.32±3.88个/视野,P<0.01)。结论转染血管内皮生长因子基因的骨髓间充质干细胞移植可改善兔心肌梗死后的心功能,其疗效明显优于单纯骨髓间充质干细胞移植及血管内皮生长因子基因治疗,可能是通过增加骨髓间充质干细胞的存活及改善梗死区的血供而起作用的。 相似文献
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Bone marrow mononuclear cell transplantation into heart elevates the expression of angiogenic factors 总被引:8,自引:0,他引:8
The expression of angiogenic factors was measured to elucidate the mechanism of angiogenesis after bone marrow stem cells transplantation. The left anterior descending coronary (LAD) artery was ligated in male Lewis rats to induce an acute myocardial infarction (AMI); of which, some rats received bone marrow mononuclear cells transplantation (BMT). The expression of cytokines and their receptors was assessed by RT-PCR. The expression of c-met was upregulated in the AMI animals and was further increased when the animals received BMT (P < 0.01). The other cytokines and their receptors remained unchanged after BMT compared with AMI samples. Normal bone marrow mononuclear cells have higher expression level of hepatocyte growth factor (HGF) than those in normal hearts. In conclusion, BMT could increase the expression of c-met. Not all angiogenic cytokines and their receptors were upregulated after BMT. The higher expression of hepatocyte growth factor in bone marrow may contribute to the upregulation of c-met. 相似文献
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Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. 总被引:14,自引:0,他引:14
Bodo E Strauer Michael Brehm Tobias Zeus Thomas Bartsch Christina Schannwell Christine Antke Rüdiger V Sorg Gesine K?gler Peter Wernet Hans-Wilhelm Müller Matthias K?stering 《Journal of the American College of Cardiology》2005,46(9):1651-1658
OBJECTIVES: Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. BACKGROUND: After acute MI, bone marrow-derived cells improve cardiac function. METHODS: We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. RESULTS: After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). CONCLUSIONS: These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation. 相似文献
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目的:探讨功能化纳米纤维支架(NFS)承载骨髓源性心肌干细胞(MCSCs)移植对大鼠心肌梗死(MI)后心功能恢复的影响,寻找一种更适合承载MCSCs治疗MI的可注射性生物材料。方法:通过单细胞克隆培养技术,从骨髓间充质干细胞中筛选具有心肌特异分化潜能的MCSCs,并固相合成自聚多肽。将24只雌性大鼠MI模型随机分为3组,即对照组、MCSCs移植组和支架承载MCSCs移植组,每组8只。细胞移植后4周,用M型超声心动图检测心功能恢复的情况。将心脏组织切片并进行Masson染色,利用图像分析检测胶原纤维的比率。采用原位荧光杂交法标记心肌组织中的Y染色体细胞,并检测心肌肌钙蛋白T(cTnT)的表达。结果:与MCSCs移植组相比,支架承载细胞移植组大鼠的心功能指数明显提高,胶原纤维比率明显减小,Y染色体阳性细胞数明显增多(P<0.05)。结论:支架承载MCSCs移植治疗MI,有利于移植细胞在受损心肌内的存活和向功能性心肌细胞分化,并可促进心功能恢复,其疗效优于单纯干细胞移植。 相似文献
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G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells 总被引:1,自引:0,他引:1
Brunner S Huber BC Fischer R Groebner M Hacker M David R Zaruba MM Vallaster M Rischpler C Wilke A Gerbitz A Franz WM 《Experimental hematology》2008,36(6):695-702
OBJECTIVE: Besides its classical function in the field of autologous and allogenic stem cell transplantation, granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI) by mobilization of bone marrow-derived progenitor cells (BMCs) and in addition by activation of multiple signaling pathways. In the present study, we focused on the impact of G-CSF on migration of BMCs and the impact on resident cardiac cells after MI. MATERIALS AND METHODS: Mice (C57BL/6J) were sublethally irradiated, and BM from green fluorescent protein (GFP)-transgenic mice was transplanted. Coronary artery ligation was performed 10 weeks later. G-CSF (100 microg/kg) was daily injected for 6 days. Subpopulations of enhanced GFP(+) cells in peripheral blood, bone marrow, and heart were characterized by flow cytometry. Growth factor expression in the heart was analyzed by quantitative real-time polymerase chain reaction. Perfusion was investigated in vivo by gated single photon emission computed tomography (SPECT). RESULTS: G-CSF-treated animals revealed a reduced migration of c-kit(+) and CXCR-4(+) BMCs associated with decreased expression levels of the corresponding growth factors, namely stem cell factor and stromal-derived factor-1 alpha in ischemic myocardium. In contrast, the number of resident cardiac Sca-1(+) cells was significantly increased. However, SPECT-perfusion showed no differences in infarct size between G-CSF-treated and control animals 6 days after MI. CONCLUSION: Our study shows that G-CSF treatment after MI reduces migration capacity of BMCs into ischemic tissue, but increases the number of resident cardiac cells. To optimize homing capacity a combination of G-CSF with other agents may optimize cytokine therapy after MI. 相似文献
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Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis 总被引:13,自引:0,他引:13
Abdel-Latif A Bolli R Tleyjeh IM Montori VM Perin EC Hornung CA Zuba-Surma EK Al-Mallah M Dawn B 《Archives of internal medicine》2007,167(10):989-997
BACKGROUND: The results from small clinical studies suggest that therapy with adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. RESULTS: Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (-5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end-systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006). CONCLUSIONS: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes. 相似文献
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Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction
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Ayach BB Yoshimitsu M Dawood F Sun M Arab S Chen M Higuchi K Siatskas C Lee P Lim H Zhang J Cukerman E Stanford WL Medin JA Liu PP 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(7):2304-2309
Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem/progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly elucidate the mechanistic contributions of c-kit+ bone marrow-derived hematopoetic stem/progenitor cells in the maintenance and repair of damaged myocardium after MI. Using c-kit-deficient mice, we demonstrate the importance of c-kit signaling in preventing ventricular dilation and hypertrophy, and the maintenance of cardiac function after MI in c-kit-deficient mice. Furthermore, we show phenotypic rescue of cardiac repair after MI of c-kit-deficient mice by bone marrow transplantation of wild-type HSPCs. The transplanted group also had reduced apoptosis and collagen deposition, along with an increase in neovascularization. To better understand the mechanisms underlying this phenotypic rescue, we investigated the gene expression pattern within the infarcted region by using microarray analysis. This analysis suggested activation of inflammatory pathways, specifically natural killer (NK) cell-mediated mobilization after MI in rescued hearts. This finding was confirmed by immunohistology and by using an NK blocker. Thus, our investigation revealed a previously uncharacterized role for c-kit signaling after infarction by mediating bone marrow-derived NK and angiogenic cell mobilization, which contributes to improved remodeling and cardiac function after MI. 相似文献
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Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions 总被引:14,自引:0,他引:14
Kuethe F Richartz BM Sayer HG Kasper C Werner GS Höffken K Figulla HR 《International journal of cardiology》2004,97(1):123-127
BACKGROUND: Experimental and preliminary clinical data suggest that transplantation of autologous bone marrow cells (BMC) may contribute to regeneration of the myocardium after acute myocardial infarction. This approach should be tested in patients with large infarctions in whom a positive effect would be most beneficial. METHODS AND RESULTS: After successful recanalization within 5.9 +/- 2.5 h and stent implantation in five patients with a large acute anterior myocardial infarction (AMI), the patients received autologous mononuclear BMCs via a balloon catheter placed into the left anterior descending artery 6.3 +/- 0.4 days after revascularization. At 3-month follow-up, no improvement was observed for left ventricular ejection fraction, regional wall motion in the infarcted zone, contractility index measured via dobutamine stress echocardiography, coronary blood flow reserve and maximal oxygen uptake, respectively. After further follow-up of 12 months, again no change of the left ventricular ejection fraction could be detected. CONCLUSIONS: Intracoronary transplantation of autologous mononuclear BMCs did not improve cardiac function in our patients with large anterior myocardial infarctions after 3 and 12 months. 相似文献
18.
A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease 总被引:1,自引:0,他引:1
Yokoyama S Fukuda N Li Y Hagikura K Takayama T Kunimoto S Honye J Saito S Wada M Satomi A Kato M Mugishima H Kusumi Y Mitsumata M Murohara T 《Journal of molecular and cellular cardiology》2006,40(1):24-34
OBJECTIVE: Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI). METHODS: BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, cardiac function was analyzed with the use of a conductance catheter, and histopathologic analysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI. RESULTS: Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI. CONCLUSION: The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease. 相似文献
19.
Masafumi Takahashi Yoji Hakamata Shin-ichi Takeda Takashi Kaneko Koichi Takeuchi Ri-Ichi Takahashi Masatsugu Ueda Uichi Ikeda Kazuyuki Shimada Eiji Kobayashi 《Cardiovascular Engineering》2003,3(2):63-69
Cell transplantation and regeneration therapy are potentially new therapeutic approaches for cardiovascular disease. Transgenic (tg) animals for reporter genes would be useful to follow the cell lineage and differentiation during development and regeneration processes. In the present study, we developed green fluorescent protein (GFP)-tg rats and evaluated them as a tool for the study of cardiomyocyte transplantation and regeneration. The myocardium and bone marrow cells derived from GFP-tg rats strongly expressed GFP. Because neonatal rat cultured cardiomyocytes also strongly expressed GFP, we transplanted GFP-tg rat-derived cardiomyocytes in a rat myocardial infarction (MI) model. Survival of GFP-tg rat-derived cardiomyocytes was confirmed. We further investigated whether bone marrow cells could differentiate into cardiomyocytes using this GFP-tg rat-derived bone marrow cells in vitro and in vivo. GFP-tg rat-derived bone marrow cells differentiated into cardiomyocyte- like cells (cardiac troponin I-expressed cells) by co-culture with wild rat cultured cardiomyocytes in vitro. Furthermore, differentiation of bone marrow cells into cardiomyocyte-like cells was observed by injection of GFP-tg rat-derived bone marrow cells in a rat MI model in vivo. These findings suggest that GFP-tg rats are a useful and valuable tool for the study of transplantation and regeneration in myocardium. 相似文献
20.
骨髓源性心肌干细胞移植治疗心肌梗死的实验研究 总被引:2,自引:0,他引:2
目的研究骨髓源性心肌干细胞(MCSC)移植对心肌梗死的治疗作用。方法通过单细胞克隆培养技术从雄性SD大鼠骨髓间充质干细胞(MMSC)中筛选MCSC。结扎雌性SD大鼠的左冠状动脉前降支,建立心肌梗死模型,1周后于梗死区边缘移植MMSC和MCSC。移植后4周,用超声心动图检测心功能变化。取心肌组织作冷冻切片,用HE和Masson染色法显示瘢痕区的组织结构变化,通过免疫组织化学染色标记血管内皮生长因子受体-1阳性(VEGFR-1^+)微血管,用图像分析系统测量瘢痕面积和微血管密度。利用原位荧光杂交标记含有Y染色体的MCSC,并检测心肌特异性肌钙蛋白T(cTnT)的表达。结果筛选的MCSC表达c—kit,心肌早期转录因子Nkx2.5呈低表达。细胞移植后4周,MCSC移植组的左室短轴缩短分数(62.9%±2.2%)和左室射血分数(32.8%±1.1%)高于MMSC移植组(分别为55.7%±1.6%和28.2%±1.6%)和对照组(分别为42.4%±2.1%和23.6%±1.2%);MCSC组心肌梗死面积比率(8.7%±0.7%)低于MMSC组(12.0%±1.1%)和对照组(16.8%±0.9%)。含有Y染色体的MCSC表达cTnT,与受体心肌相续。MCSC移植组的梗死区周围微血管密度[(101.8±6.2)条/mm^2]大于对照组[(68.4±4.9)条/mm^2],与MMSC组[(97.2±3.2)条/mm^2]比较,差异无统计学意义。结论移植入心肌梗死模型的MCSC能够分化为功能性心肌,明显改善心功能,并诱导血管新生。MCSC的移植治疗效果优于MMSC。 相似文献