自体成肌细胞移植改善兔心肌梗死后心功能的实验研究(英文)

目的:将体外培养并纯化的自体骨骼肌成肌细胞植入心肌梗死区,观察其心脏功能有无改善及改善程度,以探讨成肌细胞移植治疗的机制。方法:采用反复差速贴壁法体外培养、纯化及鉴定新西兰兔自体成肌细胞。结扎冠状动脉致局部心肌梗死后2周,分别将成肌细胞和对照的细胞培养液注入心肌梗死区,4周后观察心功能改善情况,鉴定心肌梗死边缘区毛细血管密度及植入细胞的形态。结果:体外培养获得高纯度(85.4%±6.7%)Desm in阳性的自体骨骼肌成肌细胞。经Buxco系统有创心功能测定显示自体成肌细胞移植组较对照组的左心室等容收缩期室内压最大上升速率[+dp/dtmax,(1 217.77±89.91)mmHg/s vs.(897.83±70.04)mmHg/s]和左心室等容舒张期室内压最大下降速率[-dp/dtmax,(-1 174.58±91.5)mmHg/s vs.(-753.67±69.66)mmHg/s]均有所改善。免疫组织化学和电镜证实植入的细胞为肌源性且细胞移植区域的毛细血管密度较对照组高。结论:采用反复差速贴壁法培养可在体外获得高纯度骨骼肌成肌细胞,植入成肌细胞能增加心肌收缩力,改善心功能并促进心肌梗死区域的毛细血管数量增加。

脑梗死急性期和恢复期血管内皮细胞和纤溶功能的变化

观察脑梗死急性期患者和恢复期患者的血管内皮细胞和纤溶功能的变化。应用酶标法、免疫扩散法和发色底物法对 82例脑梗死急性期患者和 12 4例脑梗死恢复期患者进行血液学观察并与 92例正常人对照。结果发现 ,与对照组比较 ,脑梗死急性期患者的血管性假血友病因子明显升高 ,6 酮 前列腺素F1α和组织型纤溶酶原激活物活性明显下降 ;脑梗死恢复期患者的纤溶酶原、组织型纤溶酶原激活物抗原和组织型纤溶酶原激活物活性明显下降 ,脑梗死急性期和恢复期患者的纤溶酶原激活物抑制剂均轻度升高。脑梗死恢复期患者的血管性假血友病因子、纤溶酶原、组织型纤溶酶原激活物抗原和组织型纤溶酶原激活物活性较脑梗死急性期患者明显下降 ,但均未恢复正常。结果提示 ,脑梗死急性期患者和恢复期患者都存在明显的血管内皮细胞和纤溶功能异常 ,临床上不仅要重视脑梗死急性期的治疗 。

骨髓间充质干细胞移植治疗脑梗死:有望产生结构与功能的双重修复作用

学术背景:成年人脑海马齿状回和嗅球等部位发现神经干细胞后,彻底改变了传统发生生物学所认为的成熟神经元一旦受损就不能再生这一观念,但神经干细胞存在取材不便、受伦理学限制及免疫排斥等缺陷。通过骨髓间充质干细胞移植治疗脑梗死,有望从组织结构功能上对坏死神经元进行修复。目的:归纳总结近年来骨髓间充质干细胞移植治疗脑梗死方面的实验研究进展。检索策略:由该论文的研究人员应用计算机检索Pubmed数据库1998-01/2006-12的相关文献,检索词"mesenchymalstemcells,cerebralinfarction,cerebralischemia,transplant",并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1998-01/2006-12的相关文献,检索词"骨髓间充质干细胞,脑梗死,脑缺血,移植",并限定文章语言种类为中文。共检索到88篇文献,对资料进行初审,纳入标准:文章所述内容应与骨髓间充质干细胞移植治疗脑梗死、脑缺血的研究相关。排除标准:重复性研究。文献评价:文献的来源主要是通过对骨髓间充质干细胞移植治疗脑梗死方面内容进行汇总分析。所选用的30篇文献中,1篇为综述,其余均为临床或基础实验研究。资料综合:①骨髓间充质干细胞具有高度自我更新和多向分化潜能,在体内外可以分化为多种细胞,近年来作为组织工程的种子细胞用于脑梗死的治疗。②骨髓间充质干细胞来源方便,体外培养扩增快速,可通过静脉、动脉、立体定位注射和腹腔注射等途径移植入脑梗死模型动物体内,并且能够迁移至受损脑组织。③骨髓间充质干细胞可能通过分泌神经营养因子,减少神经细胞凋亡,替代受损神经元,促进血管、轴突、髓鞘等再生,激活内源性神经干细胞的增殖分化等机制修复受损脑组织。④骨髓间充质干细胞可作为基因载体,通过导入外源性基因,与基因治疗相结合治疗脑梗死效果更好。结论:骨髓间充质干细胞作为种子细胞在治疗模型动物脑梗死方面已经取得一定效果,其详细机制仍有待进一步深入研究,而且在应用于临床前仍有许多理论和技术问题需要解决。

动脉粥样硬化性脑梗死患者红细胞的免疫功能改变

探讨动脉粥样硬化性脑梗死患者红细胞免疫粘附功能变化的特点。观察了86例动脉粥样硬化性脑梗死患者和63例正常对照者的红细胞免疫功能4项指标:红细胞C_(3b)受体花环率、红细胞免疫复合物花环率、血清中红细胞免疫粘附增强因子及红细胞免疫粘附抑制因子。动脉粥样硬化性脑梗死患者红细胞免疫功能变化的特点是红细胞C_(3b)受体花环率降低,红细胞免疫复合物花环率升高,同时伴有血清中红细胞免疫粘附增强因子活性降低及红细胞免疫粘附抑制因子活性增强,红细胞免疫粘附功能低下。本研究提示脑梗死患者红细胞免疫功能下降,为探讨动脉粥样硬化性脑梗死的发病与防治途径提供了依据。

益气逐瘀方改善心肌梗死大鼠心肌损伤及对miR-24/Bim通路相关蛋白表达的影响

目的:探讨益气逐瘀方参元丹对急性心肌梗死大鼠心肌损伤及miR-24/Bim通路相关蛋白表达的影响。方法:50只SD大鼠随机分为假手术组、模型组、参元丹高、中、低剂量组,每组10只,采用左冠状动脉前降支结扎法复制心肌梗死模型,参元丹高、中、低剂量组从术后第2天开始给予参元丹药液灌胃,假手术组和模型组给予等剂量生理盐水灌胃,共给药2周。治疗结束后检测大鼠血清CK、LDH水平及心肌组织miR-24基因表达,超声心动图检测左室功能,Western-blot检测心肌组织Bim、Bcl-2、Bax、caspase-9蛋白表达。结果:实验结束时,与模型组比较,参元丹高、中、低剂量组均能显著降低血清CK、LDH水平(P<0.05,P<0.01),升高心肌组织miR-24基因表达(P<0.05,P<0.01),降低左室舒张和收缩末期内径(P<0.05,P<0.01),升高左室短轴缩短率及射血分数(P<0.05,P<0.01),升高心肌组织Bcl-2蛋白表达(P<0.05),降低Bim、Bax、caspase-9蛋白表达(P<0.05,P<0.01)。结论:益气逐瘀方参元丹可能通过调控miR-24/Bim信号通路相关细胞因子蛋白表达改善心肌梗死细胞损伤。

肺梗死样梭形细胞癌一例并文献复习

目的探讨肺梗死样梭形细胞癌(ISCCL)的临床病理特征、诊断及鉴别诊断。方法分析2020年10月会诊的1例ISCCL患者的临床信息、病理组织形态以及免疫组织化学染色结果,并复习相关文献。结果患者为49岁男性。胸部CT示右肺下叶结节,于外院行右肺下叶肿块切除术。右肺下叶肿块术后病检结果显示大片梗死样区域,其间可见短梭形异型细胞,围绕血管生长,部分区域胶原纤维增生,核分裂象少见;免疫组织化学结果显示肿瘤细胞表达广谱细胞角蛋白、上皮膜抗原、波形蛋白。病理诊断为ISCCL,行肺叶切除术辅以紫杉醇联合卡铂进行化学治疗,但效果不佳,患者拒绝进一步治疗,于术后8个月因肺癌多发骨转移死亡。结论 ISCCL是一种罕见的侵袭性恶性肿瘤,形态学特征与多种肺良恶性病变容易混淆,极易误诊、漏诊,需综合分析相鉴别。

不同剂量阿司匹林在急性脑梗死治疗中的疗效比较

目的通过观察急性脑梗死患者α颗粒膜糖蛋白(CD62p)及溶酶体颗粒膜糖蛋白(CD63)表达水平,探讨以血小板活化的变化反映不同剂量阿司匹林的疗效差异。方法使用流式细胞术检测阿司匹林0.15 g、0.20 g治疗前后的CD62p、CD63阳性率,同时进行NIHSS评分。结果脑梗死组血小板CD62p、CD63阳性率显著高于对照组(P<0.01),其在阿司匹林治疗前后也有显著差异(P<0.01),但是阿司匹林0.15 g组与0.20 g组间比较无显著性差异,两个剂量组疗效比较无差异。结论阿司匹林治疗脑梗死有效,但是其0.15 g与0.20 g剂量的疗效可能无明显差异。

Biological Characteristics of Endothelial Progenitor Cell and Its Influence on Angiogenesis Improvement

Endothelial progenitor cell （EPC） is a term that refers to multiple cell types that play roles in the regeneration of the endothelial lining of blood vessels. The EPCs in bone marrow will participate in the internal circulation in a body sub- jected to the stimulation by external factors such as injury, ischemia or drug. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. Therefore, this paper reviews the sources, isolation and culture of EPCs, the factors influencing the proliferation and activity of EPCs, and the roles of EPCs in angiogenesis.

Neurogenesis by Activation of Inherent Neural Stem Cells in the Rat Hippocampus after Cerebral Infarction

Objective To investigate the changes of neural stem cells (NSCs) in the rat hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were made and rats were assigned to 6 groups: sham-operated, 1 day, 3 days, 7 days, 14 days, and 28 days after CI. The dynamic expression of bromodeoxyuridine (BrdU), polysialylated neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA-NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used to mark the differentiated NSCs. Results Compared with the controls, the number of BrdU+ cells in the hippocampus increased significantly at 1 day after CI (P<0.05), reached peak at 7 days after CI (P<0.05), decreased but still elevated compared with the controls at 14 days after CI (P<0.05), and nearly unchanged at 28 days after CI. The number of BrdU+/PSA-NCAM+ cells increased significantly at 7 days after CI (P<0.05), reached peak at 14 days after CI (P<0.05), and decreased but still elevated compared with the controls at 28 days after CI (P<0.05). The number of BrdU+/PSA-NCAM+ cells was equal to 60% of the number of BrdU+ cells in all the same period. The number of BrdU+/NeuN+ cells in the hippocampus increased significantly at 14 days after CI (P<0.05) and reached peak at 28 day after CI (P<0.05). The number of BrdU+/GFAP+cells in the hippocampus nearly unchanged after CI. Conclusion CI can stimulate the proliferation of inherent NSCs, and most proliferated NSCs may differentiate into neurons and represent neural plasticity.

Review:Cell therapy in congestive heart failure

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.

Significantly reduced function of T cells in patients with acute arterial thrombosis

Objectives To explore the intrinsic factors related to the pathogenesis of acute arterial thrombosis （AAT） and to elucidate the patho- genesis of AAT on the basis of differentially expressed genes. Methods Patients with acute myocardial infarction （AMI）, stable angina （SA） and healthy controls （n = 20 per group） were recruited, and the whole human genome microarray analysis was performed to detect the differentially expressed genes among these subjects. Results Patients with AMI had disease-specific gene expression pattern. Biological functional analysis showed the function of T cells was significantly reduced, the mitochondrial metabolism significantly decreased, the ion metabolism was abnormal, the cell apoptosis and inflammatory reaction increased, the phagocytosis elevated, the neutrophil-mediated immunity increased and the post-traumatic repair of cells and tissues increased in AMI patients. The biological function in SA group and healthy controis remained stable and was comparable. Conclusions The reduced function ofT cell gene models in AAT showed the dysfunction of the immune system. The pathogenesis of AAT may be related to the inflammatory reaction after arterial intima infection caused by potential pathogenic microorganisms.

Short- and Long-term Therapeutic Efficacies of Intravenous Transplantation of Bone Marrow Stem Cells on Cardiac Function in Rats with Acute Myocardial Infarction:A Meta-analysis of Randomized Controlled Trials

Objective To investigate the short- and long-term therapeutic efficacies of intravenous transplantation of bone marrow stem cells(MSCs) in rats with experimental myocardial infarction by metaanalysis.Methods Randomized controlled trials were systematically searched from Pub Med,Science Citation Index(SCI),Chinese journal full-text database(CJFD) up to December 2014.While the experimental groups(MSCs groups) were injected MSCs intravenously,the control groups were injected Delubecco's minimum essential medium(DMEM) or phosphate buffered saline(PBS).Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs.Weighted mean differences(WMD) and 95% confidence intervals(CI) were calculated for outcome parameters including ejection fraction(EF) and fractional shortening(FS),which were measured by echocardiogram after intravenous injection and analyzed by Rev Man 5.2 and STATA 12.0.Results Data from 9 studies(190 rats) were included in the meta-analysis.As compared to the control groups,the cardiac function of the experimental groups were not improved at day 7(EF:WMD=0.08,95%CI-1.32 to 1.16,P>0.01; FS:WMD=-0.12,95%CI-0.90 to 0.65,P>0.01) until at day 14 after MSCs' transplantation(EF:WMD=10.79,95%CI 9.16 to 12.42,P<0.01; FS:WMD=11.34,95%CI 10.44 to 12.23,P<0.01),and it lasted 4 weeks or more after transplantation of MSCs(EF:WMD=13.94,95%CI 12.24 to 15.64,P<0.01; FS:WMD=9.64,95%CI 7.98 to 11.31,P<0.01).Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.

MicroRNA-15a/b are up-regulated in response to myocardial ischemia/reperfusion injury

Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion （I/R） injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation （H/R）.Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo （24.4％ ± 9.4％ vs.2.2％ ± 1.9％,P ＜ 0.01,n =5） and in vitro （14.12％ ±0.92％ vs.2.22％ ± 0.08％）.The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.

Effects of nerve growth factor on delayed afterdepolarization and triggered activity in the infarcted ventricle of rabbit model

The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor （NGF） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks （HMI group, n=9）. Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion （HMI＋NGF group, 400 U/day for 8 weeks, n=8）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI＋NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF＋HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI＋NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.

Ion mechanism of isoproterenol on delayed afterdepolarization and triggered activity in the infarcted ventricle

Objectives This study aimed at investigating the cellular mechanism of isoproterenol （ISO） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk （healed myocardial infarction, HMI）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and IC,_L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of I6 and calcium influxing

Cardioprotective effects of Chinese herbal medicine Braintone on myocardial infarction in rats

Recently, we reported the unique effects of cerebral protection of the Chinese herbal medicine-Braintone （a formulation containing Radix Rhodiola, Folium Ginkgo, Radix Notoginseng and Rhizoma Ligustici Chuanxiong）, also known as Remembrance. In the present study, we tested the hypothesis that Braintone may extend cardioprotective effects on ischemic myocardium in Wistar rats. Animal model was created by ligating of left descending coronary artery. Mortality rate and infarct volume were assessed. In addition, capillary density, antioxidant enzymes, apoptosis modulators and VEGF, eNOS mRNA expression level were investigated to reveal the underlying mechanisms. Treatment with Braintone reduced mortality rate from 41.7% to 22.2% associate with notable diminished infarct volume （30.4%±9.0% vs 18.0%±3.0%）. Braintone also acted as antioxidant agent for preserving the activities of catalase （13.07±0.48 U vs 9.71±0.44 U in vehicle, P〈0.01）. Furthermore, Braintone dramatically boosted the expression levels of anti-apoptotic genes Bcl-2 and Bcl-xl （1.43-, 2.30-fold, P〈0.01） as compared to vehicle group and significantly down-regulated the expression level ofpro-apoptotic gene Bax （0.84-fold, P〈0.01） while slightly inhibited Caspase-9 and Caspase-3 signals. Moreover, higher mRNA expression levels of VEGF and eNOS were observed in Braintone group consisting with a remarkable raise of capillary density （46.0±13.3 vs 27.4±12.6, P〈0.01） in myocardium. The findings indicated that Braintone markedly attenuate myocardial damage induced by ischemic insults in vivo. Braintone may confer cardioprotection via scavenging free radicals, inhibiting cardiomyocytes apoptosis and promoting angiogenesis in ischemic region.

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progenitor cell(CPC)activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction(MI).This study aims to explore the role and possible mechanisms of CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation.AM1241 also decreased serum levels of MDA,TNF-αand IL-6 after MI.In addition,AM1241 can ameliorate left ventricular ejection fraction and fractional shortening,and reduce fibrosis.Moreover,AM1241 treatment markedly increased p-Akt and HO-1 expression,and promoted Nrf-2 nuclear translocation.However,PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241.In conclusion,AM1241 could induce myocardial regeneration and improve cardiac function,which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.

Cardioprotective effects of combination of notoginseng total saponins and safflower total flavonoids against myocardial infarction in rats

In this study, the cardioprotective mechanism of the combination of notoginseng total saponins and safflower total flavonoids（CNS） was investigated due to its excellently efficacy against myocardial infarction（MI） in rats. After the left anterior descending coronary artery（LADCA） ligation, rats were orally administered with CNS for 7 consecutive days. CNS prevented MI-induced pathophysiological changes and significantly decreased plasma levels of myocardial enzymes, including creatine kinase MB isoenzyme（CK-MB）, lactate dehydrogenase（LDH） and aspartate aminotransferase（AST）. Further investigation revealed that CNS attenuated the production of inflammatory factors in plasma, including tumor necrosis factor-alpha（TNF-α）, interleukin-6（IL-6） and interleukin-1β（IL-1β）. Moreover, CNS treatment decreased the expression of caspase-3 at the mR NA level in infarct tissue. Our findings demonstrated that the anti-inflammatory and anti-apoptotic properties of CNS might confer its cardioprotection against MI in rats.

Affects of different access routes on autologous satellite cell implantation stimulating myocardial regeneration

To study the effect of different access routes on autologous satellite cell implantation to stimulate myocardial regeneration Methods Satellite cells were procured from skeletal muscle (gluteus max) of adult mongrel canine, cultured, proliferated and labeled with 4’,6 diamidino 2 phenylindone (DAPI) in vitro The cells were autologously implanted into the site of acute myocardial infarction by local injection or perfusion through the ligated distal left anterior descending coronary artery Specimens were harvested 2, 4 and 8 weeks later for histological study Results The labeling efficiency of satellite cells with DAPI was close to 100% Fluorescent cells were found at the infarcted zone, papillary muscle and local injection site Some of these cells had progressively differentiated into striated muscle fibers connected to intercalated discs The infant cells appeared different from the mature myocardium under an electron microscope Satellite cells implanted by perfusion through the coronary artery were arranged in order of consistency with host myocardial fibers The satellite cells, implanted by local injection, were found growing in a disordered way Conclusion Satellite cells, implanted by coronary artery perfusion, can progressively differentiate into striated muscle fibers, arranging in order and disseminating over the infarcted zone This approach seems more favorable for the recovery of myocardial contractile function than that of local injection

Timing of transplantation of autologous bone marrow derived mesenchymal stem cells for treating myocardial infarction

It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion.However,the adverse inflammatory environment,with its high oxidative stress,might be deleterious if cells are administered too early after reperfusion.Here we highlight several aspects of the timing of intracoronary stem cell therapy.Our results showed that transplantation of bone marrow mesenchymal stem cells at 2 4 weeks after myocardial infarction is more favorable for reduction of the scar area,inhibition of left ventricular remodeling,and recovery of heart function.Coronary injection of autologous bone marrow mesenchymal stem cells at 2 4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.