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田涛  马宾 《心脏杂志》2012,24(1):117-119,137
溶栓、经皮冠状动脉介入治疗及常规药物治疗可挽救许多急性心肌梗死患者的生命,但不能从根本上恢复心肌细胞数量。骨髓间充质干细胞(BM-MSCS)是骨髓中一种具有多向分化潜能的细胞,可被诱导分化为心肌样细胞,改善梗死区的血液供应及心肌重构,为心肌梗死的治疗带来了新的希望。本文就BM-MSCS移植治疗心肌梗死的方式,移植的时机及临床应用等方面作一综述。  相似文献   

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心肌梗死(myocardial infarction,MD是由于冠状动脉循环改变引起冠状血流和心肌需求之间不平衡而导致的心肌损害,是临床上一种严重的缺血性心脏病(ischemic heart isease,IHD)。梗死的心肌细胞逐渐被瘢痕组织取代,由于瘢痕组织缺乏弹性,难以满足心脏收舒功能的要求,  相似文献   

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目的:探讨骨髓间充质干细胞(MSCs)移植对心肌梗死大鼠脾脏淋巴细胞体外杀伤效应的影响。方法:复制大鼠急性心肌梗死(AMI)模型,采用心外膜注射方法移植MSCs或PBS液,另取正常组、假手术组作对照。分别于手术后第1周、第2周和第4周末提取脾脏淋巴细胞,并与乳鼠心肌细胞共培养,采用结晶紫法检测淋巴细胞的杀伤效应。结果:手术后第2和4周末,AMI加PBS组脾脏淋巴细胞杀伤效应分别为(32.31±7.23)%、(47.20±5.13)%,较正常组[(21.95±4.65)%,(22.13±5.08)%]和假手术组[(22.21±5.43)%,(24.21±5.40)%]明显增强(均P<0.05)。相对于AMI加PBS组,AMI加MSCs组第2、4周末在一定程度上抑制了淋巴细胞的杀伤效应,分别为(26.14±5.15)%、(34.28±6.13)%,与AMI加PBS组的同时间比较,均P<0.05。结论:MSCs移植可抑制心肌梗死大鼠脾脏淋巴细胞对心肌细胞的杀伤效应。  相似文献   

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骨髓间质干细胞移植治疗急性心肌梗死的实验研究   总被引:1,自引:0,他引:1  
目的 研究同种异体骨髓间质干细胞(bone marrow mesenchymak stem cells MSCs)移植至梗死心肌后对兔的一般情况、心功能、梗死面积和血管新生的影响.方法 开胸结扎冠状动脉左前降支建立急性心肌梗死动物模型,将5-溴脱氧尿核苷(bromodeoxyuridine,BrdU)标记的MSCs注入心肌梗死区.测定各组手术前后体重和心功能并取出心脏作相关检查.结果 与急性心肌梗死组比较,MSCs组术后一般情况好,6周时体重明显增加(P<0.05),术后3周、6周左心室射血分数(left ventricular ejection fraction,LVEF)均明显增加(P<0.05),梗死面积明显缩小(P<0.05),毛细血管数目显著增多(P<0.01).MSCs组心肌梗死区可见BrdU阳性细胞,电镜下可见不成熟的心肌样细胞.结论 同种异体MSCs移植治疗急性心肌梗死除提高心功能外,尚可改善兔子的一般情况,增加体重.  相似文献   

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目的:探讨同种异体骨髓间充质干细胞(MSCs)心内膜移植治疗小型猪急性心肌梗死的疗效。方法:分离、纯化、扩增培养小型猪MSCs;开胸结扎第1与第2对角支间前降支中段形成急性前壁心肌梗死的动物模型,心肌梗死后2~3周经心内膜注射移植DAPI标记的同种异体MSCs,心肌梗死前、后及移植后3个月行超声心动图及生化检查,并取梗死周围心肌组织冰冻切片及苏木精-伊红染色,免疫荧光法鉴定结蛋白(desmin)和心肌肌钙蛋白I(cTnI)的表达。结果:每40ml骨髓液经2~3周传3代平均获得(3.81±0.09)×107个细胞,移植后3个月左室射血分数较心肌梗死后及对照组改善明显,分别为(56.7±0.8)%,(40.1±1.2)%,(34.9±0.9)%(均P<0.05),肝肾功能、血糖及血气分析正常,3个月冰冻切片可见坏死心肌周围细胞核蓝染的移植细胞,免疫组化提示desmin及cTnI表达阳性。结论:同种异体MSCs经心内膜移植安全有效,心功能明显改善。  相似文献   

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The goal of the study was to examine if allogenic mesenchymal stem cell (MSC) transplantation is a useful therapy for acute myocardial infarction (AMI). Buffer (control; group C, n = 41), MSCs of male ACI rats (allogenic; group A, n = 38, 5 × 106), or MSCs of male LEW rats (syngenic; group S, n = 40, 5 × 106) were injected into the scar 15 min after myocardial infarction in female LEW rats. After 28 days, fractional left ventricular shortening significantly increased in groups A (21.3 ± 1.7%, P = 0.0467) and S (23.2 ± 1.9%, P = 0.0140), compared to group C (17.1 ± 0.9%). Fibrosis in groups A and S was significantly lower. Quantitative PCR of the male-specific sry gene showed disappearance of donor cells within 28 days (5195 ± 1975 cells). Secretion of vascular endothelial growth factor (VEGF) by MSCs was enhanced under hypoxic conditions in vitro. In groups A and S, the plasma VEGF concentration, VEGF level, and capillary density in recipient hearts increased after 28 days. Flow cytometry revealed the absence of B7 signal molecules on MSCs. A mixed lymphocyte reaction showed that ACI MSCs failed to stimulate proliferation of LEW lymphocytes. After 1 day after cell transplantation, transient increases in interleukin-1 beta and monocyte chemoattractant protein-1 in recipient hearts were enhanced in group A, with macrophage infiltration at the injection site. T cells remained at the level of normal tissue in all groups. We conclude that allogenic MSC transplantation therapy is useful for AMI. The donor MSCs disappear rapidly, but become a trigger of VEGF paracrine effect, without induction of immune rejection.  相似文献   

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骨髓基质干细胞(MSC)具有良好的分化潜能,能分化为心肌细胞和血管内皮细胞,从而再生心肌和血管,重塑心肌结构,改善心肌收缩功能和室壁顺应性,促进血管再生,建立有效冠脉侧枝循环,提高心脏整体功能,既改善了血供又解决心肌细胞数量减少这一心力衰竭的根本原因;而自体移植不受来源限制,取材方便、创伤小,更新率低而代谢活力高,由其分化来的心肌细胞能与周围受体肌肉细胞进行有效的电机械偶合,容易通过转基因技术获得目标基因并在体内外长期表达,也不存在免疫排斥和基因突变等安全性问题,因此作为心肌梗死(MI)疾病治疗的新途径有着广阔的前景.现就近年来国内外MSC自体移植在治疗MI方面的研究进展作一综述.  相似文献   

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目的 探讨骨髓间充质干细胞(MSC)对梗死心肌胶原重构的调节作用。方法 采用结扎冠状动脉前降支的方法复制大鼠心肌梗死(MI)模型,随机分为假手术组(仅穿线不结扎冠状动脉,n=8)、MI+ PBS组(结扎冠状动脉+心肌注射PBS溶液,n=8)和MI+ MSC组(结扎冠状动脉+心肌注射MSC,n=8)。通过心脏超声检查、血液动力学检查和组织学染色方法分别检测左心室射血分数(LVEF)、短轴缩短率(FS)、左心室收缩末压力(LVSP)、左心室舒张末压力(LVEDP)、左心室压最大升降速率(±dp/dtmax)、心肌梗死面积和梗死扩张指数等指标,评价MSC对大鼠心功能及心室重构的影响。同时采用免疫组化、RT-PCR、Western blot等方法,测量胶原蛋白表达情况。结果 (1)MI大鼠心室重构和心脏功能指标的检测结果:MI+ MSC组大鼠心肌梗死面积显著小于MI+ PBS组[(38.27±2.70)%比(46.20±3.17)%,t=5.386,P<0.001],FS显著高于MI+ PBS组[(29.98±4.50)%比(23.43 ±3.34)%,t=-3.305,P=0.005],LVSP显著高于MI+ PBS组[(113.63±10.81)mm Hg(1 mm Hg=0.133 kPa)比(99.25±16.76)mm Hg,P<0.05],LVEDP显著低于MI+PBS组[(12.10±4.28) mm Hg比(20.08±4.26) mm Hg,P<0.05],+dp/dtmax显著高于MI+ PBS组[(4616.63±363.34)mum Hg/s比(3912.75±248.79) mm Hg/s,P<0.05],- dp/dtmax显著高于MI+ PBS组[(4254.63±324.34) mm Hg/s比(3530.88±309.71)mm Hg/s,P<0.05]。(2)Ⅰ型和Ⅲ型胶原蛋白表达水平的检测结果:MI+ MSC组大鼠梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著高于MI+ PBS组,而非梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著低于MI+ PBS组(P均<0.05)。结论 MSC通过促进MI大鼠梗死区胶原蛋白修复性合成,减少非梗死区胶原蛋白沉积,从而抑制心室重构,改善心脏功能。  相似文献   

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目的:观察超声破裂微泡介导的骨髓间充质干细胞(BM-MSCs)移植对兔急性心肌梗死后心室重构和血管新生的影响。方法:取日本大耳白兔52只随机均分为4组:超声组(US组):采用超声波经兔胸壁辐照;微泡组(MB组):经静脉输注微泡造影剂;超声微泡联合组(US+MB组):经静脉输注微泡造影剂后采用超声辐照破裂微泡;空白对照组:不予超声及微泡处理。各组取骨髓体外培养BM-MSCs。结扎兔左冠脉前降支建立急性心肌梗死(AMI)模型,分别于再灌注1h后对各组动物采取超声或微泡处理后(对照组不予处理),经梗死相关动脉注射BM-MSCs悬液。术后24h和4周,测量各组兔左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)、室间隔厚度(IVST)和左室后壁厚度(LVPWT)。术后4周,处死动物检测各组兔左心室质量(LVM)、左心室质量指数(LVMI)、兔新生血管数目和血管内皮生长因子(VEGF)浓度。结果:术后4周,与US组、MB组和空白对照组相比,US+MB组LVEDd[(12.77±0.65)mm、(12.97±1.00)mm、(12.78±0.71)mm比(11.71±0.54)mm]、LVESd[(9.63±0.57)mm、(9.92±0.90)mm、(9.69±0.51)mm比(8.39±0.32)mm]、IVST[(2.69±0.11)mm、(2.65±0.14)mm、(2.63±0.10)mm比(2.48±0.07)mm]和LVPWT[(2.74±0.19)mm、(2.66±0.12)mm、(2.68±0.16)mm比(2.51±0.11)mm]明显减小(P<0.05或<0.01),LVM[(5931.76±120.61)mg、(6022.35±116.87)mg、(6076.28±122.73)mg比(4930.66±172.30)mg]及LVMI[(2.17±0.19)mg/g、(2.24±0.07)mg/g、(2.33±0.25)mg/g比(1.83±0.01)mg/g]明显降低(P<0.01),新生血管数目[(4.00±1.61)个、(4.20±1.23)个、(4.18±1.72)个比(8.82±2.52)个]明显增多(P<0.01),VEGF浓度[(0.33±0.17)μg/g、(0.32±0.08)μg/g、(0.29±0.05)μg/g比(0.65±0.24)μg/g]明显升高(P<0.01)。结论:超声微泡破裂介导的BM-MSCs移植可提高梗死心肌VEGF表达,促进血管新生,改善心肌梗死后心室重构,提高心脏功能。  相似文献   

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目的:比较经心外膜、静脉移植骨髓间充质干细胞(MSCs)治疗大鼠急性心肌梗死(AMI)的效果,为临床选择移植方法提供依据。方法:体外获取、培养大鼠骨髓MSCs。建立AMI模型,分别经心外膜、静脉移植5-溴脱氧尿嘧啶(BrdU)标记的MSCs。移植3周后超声测算左心室射血分数(LVEF)、短轴缩短率(FS);右颈总动脉插管检测血流动力学指标;免疫组化分析心肌内MSCs。结果:静脉移植组、心外膜移植组LVEF、FS较对照组均升高(P<0.05),心外膜移植组比静脉移植组升高更明显(P<0.05)。静脉移植组、心外膜移植组左心室收缩压、压力变化上升及下降速率最大值升高,左心室舒张末期压降低,心外膜移植组的变化比静脉移植组更明显(P<0.05)。心外膜移植组梗死心肌内BrdU阳性的MSCs数多于静脉移植组。结论:经心外膜移植MSCs治疗AMI的效果优于静脉移植途径。  相似文献   

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心肌梗死可引起心肌细胞的丢失,进而引起心脏功能的下降,是心力衰竭最主要的病因。骨髓间充质干细胞(BM—MSCs)是一类具有横向分化为各系统器官和组织能力的干细胞,能补充丢失的心肌细胞并通过旁分泌等机制增强心功能,为心肌梗死提供一种全新的治疗方法,极具发展潜力。本文对BM—MSCs的分离培养、诱导因素、移植以及临床研究等方面进行了综述。  相似文献   

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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   

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Background

We previously reported that amniotic mesenchymal stem cells (AMMs) possess high angio-vasulogenic properties. In this study, we investigated the chemotactic abilities of AMMs for improved cardiac function and regenerative angiogenesis.

Methods

The expressions of chemotactic and angiogenic genes were determined by qRT-PCR. Myocardial infarction (MI) was induced in NOD/SCID mice and cells were directly transplanted into the border regions of ischemic heart tissue. Immunohistochemical analysis was also conducted.

Results

AMMs significantly expressed the representative chemotactic factor GCP-2, NAP-2 as well as angiogenic factor Hif-1a. AMMs also highly expressed the chemokine receptors CCR2, CCR3 and CCR5. AMM transplantation improved left ventricular function, capillary density, angiogenic cytokine levels, angiopoetin (Ang)-1 and vascular endothelial growth factor (VEGF-A) levels in affected tissue. Immunohistochemical assaying also revealed increased engraftment and endothelial phenotypes.

Conclusion

Our findings suggest that due to elevated survival and related chemotactic potential, AMMs are a promising stem cell source for the treatment of ischemic cardiovascular disease.  相似文献   

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目的探讨静脉移植缺血预处理的间充质干细胞(MSCs)对梗死心肌的修复作用。方法选择纯种大白兔46只制作心肌梗死模型,分为缺氧预处理MSCs移植组(A组)、非缺氧预处理MSCs移植组(B组)和对照组,于心肌梗死后30d分别检测心功能、梗死心肌的形态学变化以及新生毛细血管密度。结果与对照组比较,A、B组左心室收缩末期内径、舒张末期内径降低,心功能提高,室壁厚度增加,心肌梗死面积缩小,梗死区和梗死边缘区新生毛细血管密度增加(P〈0.05)。结论MSCs移植治疗兔心肌梗死可改善心功能、缩小梗死面积、增加梗死心肌新生毛细血管密度,经缺氧预处理的MSCs移植治疗更有优势。  相似文献   

16.
目的:研究急性心肌梗死(AMI)患者骨髓间充质干细胞(MSC)生物学特性的改变。方法:取AMI患者和对照组骨髓的贴壁细胞,测定其生长曲线和倍增时间,流式细胞仪检测其免疫表型,进行纤维母细胞集落形成单位(CFUF)计数,体外诱导成脂肪和成骨,以油红O及VonKossa染色证实。结果:这些细胞呈梭形贴壁生长,CD105、CD44、CD29、Flk1均阳性,AMI组细胞倍增时间长于对照组[(61.2±4.6)∶(55.1±5.2)h],CFUF低于对照组[(10.2±1.9)∶(13.3±2.9),P<0.05],2组MSC细胞均可成脂肪、成骨。结论:AMI组MSC增殖能力较对照组弱,MSC的异常可能是AMI患者易患动脉粥样硬化原因之一。  相似文献   

17.
目的观察骨髓间充质干细胞(MSCs)经冠脉移植对急性心肌梗死后心功能的影响。方法24只日本大耳白兔,随机分为MSCs移植组(n=12)和培养液对照组(n=12)。从兔股骨抽取骨髓,体外培养MSCs。通过结扎左冠前降支建立急性心肌梗死模型。冠脉结扎后7d,细胞移植组和对照组直接经冠脉注入MSCs和培养液。于心肌梗死前、细胞移植前、细胞移植后1、2和4周对兔进行超声心动图检查。移植后4周处死动物,进行BrdU和第Ⅷ因子相关抗原免疫组化检测。结果移植后2周,MSCs移植组在射血分数(LVEF)和左室收缩末直径(LVESD)方面与移植前和对照组相比有显著改善(P<0.05);移植4周后,LVEF、LVESD和左室舒张末直径(LVEDD)在MSCs移植组与移植前及对照组相比均有显著改善(P<0.05)。免疫组化检测发现,MSCs移植组BrdU染色阳性,血管计数较对照组明显增多(P<0.01)。结论经冠脉移植的MSCs可在梗死区心肌内存活并逐渐分化成心肌样细胞,促进毛细血管生成,显著改善心功能。  相似文献   

18.
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   

19.

Background

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.

Methods

Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.

Results

LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005).

Conclusion

PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.  相似文献   

20.
AIMS: Recent data suggest that the administration of bone marrow-derived stem cells (BMSC) might improve myocardial perfusion and left ventricular (LV) function after acute myocardial infarction (AMI). The aim of this study was to assess spontaneous mobilization of BMSC expressing the haematopoietic and endothelial progenitor cell-associated antigen CD34+ after AMI and its relation to post-infarction remodelling. METHODS AND RESULTS: Peripheral blood concentration of CD34+ BMSC was measured by flow cytometry in 54 patients with AMI, 26 patients with chronic stable angina (CSA), and 43 normal healthy subjects. In patients with AMI, LV function was measured by 2D-echocardiography. Eighteen AMI patients were reassessed at 1 year. BMSC concentration was higher in patients with AMI (mean peak value: 7.04+/-6.27 cells/microL), than in patients with CSA (3.80+/-2.12 cells/microL, P=0.036) and in healthy controls (1.87+/-1.52 cells/microL, P<0.001). At multivariable analysis statin use (P<0.001), primary percutaneous intervention (P=0.048) and anterior AMI (P=0.05) were the only independent predictors of increased BMSC mobilization after AMI. In the 28 patients without subsequent acute coronary events reassessed at 1 year follow-up, CD34+ cell concentration was an independent predictor of global and regional improvement of LV function (r=0.52, P=0.004 and r=-0.41, P=0.03, respectively). CONCLUSION: AMI is followed by enhanced spontaneous mobilization of BMSC, in particular, in patients on statin therapy and following a primary percutaneous intervention. More importantly persistent spontaneous mobilization of BMSC might contribute to determine a more favourable post-AMI remodelling.  相似文献   

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