肾上腺髓质素基因转染增强骨髓间充质干细胞移植对心肌梗死大鼠心室重构及心功能的影响

目的： 研究肾上腺髓质素（ADM）基因转染增强骨髓间充质干细胞（MSCs）移植对心肌梗死大鼠心室重构及心功能的治疗作用。方法：贴壁法体外分离、扩增培养大鼠骨髓间充质干细胞,用X-gal染色测含ADM基因的重组腺病毒(Ad-ADM)对MSCs感染率,ELISA检测Ad-ADM转染后细胞上清液ADM的含量。通过结扎左冠状动脉前降支制备大鼠心肌梗死模型;以DAPI标记细胞通过心肌局部注射移植MSCs;采用生理记录仪测量大鼠的心功能,荧光显微镜观察移植细胞在心脏存活及分布,免疫组化检测ADM在心肌梗死区的表达及心梗区血管密度;天狼猩红染色检测胶原含量,用偏振光显微镜分析Ⅰ/Ⅲ型胶原比率。结果：重组腺病毒对MSCs的转染率与病毒感染复数（MOI）具有量效关系,MOI为150时细胞的感染率达95.4%;转染Ad-ADM后,MSCs可有效表达ADM,7 d时达到表达高峰,与对照组相比明显增加［(26.53±1.42 vs 1.34±0.08) ng/L,P＜0.05］,15 d后与空白对照组无差别［（2.20±1.44 vs 1.52±0.33) ng/L,P＞0.05］;在受体大鼠的心脏切片上有DAPI标记的移植细胞的存活;与对照组及其它组相比,ADM基因修饰的MSCs组心肌梗死区ADM的表达增加;与对照组比较,单纯细胞移植组心梗区新生血管密度增高（P＜0.01）;而与单纯MSCs移植组及单纯Ad-ADM注射组比较,ADM基因修饰的MSCs移植组梗死区血管密度增高更明显（P＜0.05）;单纯MSCs移植组能降低梗死区Ⅰ/Ⅲ型胶原比率（P＜0.01）,并能改善左室功能;与单纯细胞组比较ADM基因修饰的MSCs移植组梗死区Ⅰ/Ⅲ型胶原比率降低更明显（P＜0.05）,而左室功能改善更多。结论：ADM转染的MSCs移植可能通过局部ADM表达的增加,增强MSCs移植的血管新生作用及降低梗死区Ⅰ/Ⅲ型胶原比率,从而增强单纯MSCs细胞移植改善心功能的作用。     

血管内皮生长因子基因修饰骨髓间充质干细胞移植心肌梗死大鼠： 高压氧干预促进治疗性血管生成

背景：骨髓间充质干细胞移植入缺血心肌后梗死区周边心肌的缺血、缺氧、炎性反应、细胞凋亡等病理变化严重影响到移植骨髓间充质干细胞的存活,而高压氧能显著改善其缺氧状态。 目的：对心肌梗死模型大鼠缺血心肌局部移植血管内皮生长因子修饰的骨髓间充质干细胞,在移植后对大鼠进行高压氧干预,探讨其对骨髓间充质干细胞移植后所获得的治疗性血管生成效应的影响。 方法：将真核表达载体pcDNA3.1(-)/人血管内皮生长因子165转染大鼠骨髓间充质干细胞,再移植至心肌梗死模型大鼠的缺血区组织,移植前细胞行CM-DiI标记。移植后2周每日对大鼠行高压氧治疗干预。移植1个月后行心脏B超测量其左室射血分数,组织化学苏木精-伊红染色和Ⅷ因子染色并评价新生血管密度。 结果与结论：CM-DiI能有效标记骨髓间充质干细胞,标记率近100%。细胞移植1个月后高压氧干预的大鼠射血分数、再生血管密度较均明显增高(P < 0.05)。证实,高压氧干预能显著促进移植血管内皮生长因子基因修饰的骨髓间充质干细胞的心肌梗死大鼠所获得的治疗性血管生成作用,对心脏功能有明显改善作用。     

血管内皮生长因子基因转染骨髓间充质干细胞同种异体移植治疗大鼠急性心肌梗死

目的探讨同种异体血管内皮生长因子(VEGF)基因转染的骨髓间充质干细胞(MSCs)在大鼠梗死心脏局部存活、分化及对心功能的影响;明确同种异体干细胞及VEGF基因转染干细胞移植治疗急性心肌梗死(AMI)的可行性及效果。方法雄性SD大鼠30只,随机分为单纯注射培养基对照组、MSCs治疗组及VEGF基因转染MSCs治疗组。分离纯化雄性Wistar大鼠骨髓间充质干细胞(rMSCs),于左冠状动脉前降支结扎1h后植入到SD大鼠心组织,移植4周后检测心功能并取心脏行组织染色检查。结果异体大鼠MSCs可在梗死心组织定居、生存;免疫组化检测MSCs转化为心肌细胞及血管内皮细胞;与对照组比较VEGF基因转染异体细胞移植组左室射血分数升高(P<0.05),梗死边缘区心肌面毛细血管数目明显增加(P<0.05)。结论同种异体VEGF基因转染MSCs移植治疗AMI可行、有效。     

龟板促骨髓间充质干细胞肝脏归巢的作用研究

目的 探讨龟板饲养对移植骨髓间充质干细胞(MSCs)肝脏归巢的作用.方法 密度梯度离心法分离、培养大鼠MSCs,带绿色荧光蛋白腺病毒转染标记移植MSCs,激光共聚焦检测肝脏组织MSCs分布,Western blot检测肝脏肝细胞生长因子(HGF)蛋白及MSCs c-met蛋白表达,携带siRNA腺病毒转染下调c-met表达.结果 龟板饲养较普通饮食明显增加移植MSCs肝脏归巢(P＜0.05);同时,龟板饲养增加大鼠肝脏HGF蛋白表达,阻断HGF/c-met可部分逆转龟板促MSCs归巢的作用.结论 龟板饲养可能通过HGF/c-met轴促MSCs向肝脏组织归巢.     

静脉及心肌注射骨髓间充质基质细胞未能改善慢性心肌梗死大鼠的心脏功能

背景：有多项研究证明,经静脉或经心肌表面注射移植间充质基质细胞促进了急性心肌梗死后心功能的改善。然而,目前尚缺乏有关经静脉联合经心肌注射移植间充质基质细胞对慢性心肌梗死心脏功能影响的研究。 目的：探讨静脉联合心肌注射骨髓间充质基质细胞对慢性心肌梗死模型大鼠心脏功能的影响及其机制。 方法：体外培养扩增Lewis大鼠的骨髓间充质基质细胞。将3×10⁶ BrdU标记过的骨髓间充质基质细胞分别经股静脉和经心肌表面注射移植于慢性心肌梗死模型大鼠,对照组注射等量PBS。4周后检测两组大鼠心功能的变化,并对大鼠心脏组织行免疫组化染色,观察细胞分化情况及毛细血管数量。 结果与结论：骨髓间充质基质细胞移植4周后,细胞移植组与对照组心功能无明显差别,免疫组化染色提示存留于心肌组织内的移植细胞未分化为心肌细胞,心梗瘢痕区血管密度在细胞移植组和对照组间没有明显差别。结果表明经静脉联合经心肌注射骨髓间充质基质细胞未能改善慢性心肌梗死模型大鼠的心脏功能。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Livin基因修饰的骨髓间充质干细胞移植治疗对急性心肌梗死大鼠心功能的影响

 目的: 探讨livin修饰的骨髓间充质干细胞(MSCs)移植改善急性心肌梗死大鼠心功能的作用及livin和促凋亡蛋白caspase-3、caspase-7、caspase-9在感染后的表达情况。方法: 通过全骨髓培养法分离培养骨髓间充质干细胞,感染携带livin基因的重组腺病毒后用流式检测其对MSCs凋亡的影响。通过Western blot法分别检测livin、caspase-3、caspase-7和caspase-9的蛋白表达情况。采用冠状动脉左前降支结扎法建立心肌梗死模型,然后实验分4组进行:无胎牛血清的DMEM组;单纯干细胞治疗组(MSCs组);空载腺病毒转染干细胞组(rAd-control/MSCs)组;livin基因转染干细胞组(rAd-livin/MSCs组)。1个月后采用生理仪记录各组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dp/dt_max)和左室内压最大下降速率(-dp/dt_max)来评价大鼠心功能。结果: rAd-livin/MSCs组凋亡率较MSCs组和rAd-control/MSCs组显著降低(P<0.05);rAd-livin/MSCs组抗凋亡蛋白livin明显上升(P<0.05),促凋亡蛋白caspase-3、caspase-7及caspase-9表达显著下降(P<0.05);细胞移植后1个月,rAd-livin/MSCs组心功能比MSCs组改善更明显(P<0.05)。结论: rAd-livin感染MSCs后可促进抗凋亡蛋白livin的表达,同时降低促凋亡蛋白caspase-3、caspase-7和caspase-9的表达及细胞凋亡率。rAd-livin/MSCs移植能进一步改善心肌梗死大鼠心功能。     

骨髓间充质干细胞条件培养液对H2O2损伤大鼠心肌细胞的保护

背景：间充质干细胞移植可以降低心肌梗死面积、改善心功能,目前多数认为间充质干细胞分泌生物因子起主要作用。 目的：观察骨髓间充质干细胞条件培养液对过氧化氢诱导新生大鼠心肌细胞凋亡的影响。 方法：分离培养并鉴定骨髓间充质干细胞和新生大鼠心肌细胞,制作骨髓间充质干细胞条件培养液以及过氧化氢损伤新生大鼠心肌细胞模型,实验分为4组：对照组、模型组、骨髓间充质干细胞条件培养液组以及骨髓间充质干细胞条件培养液+ PI3K 抑制剂处理组。以ELISA检测乳酸脱氢酶活性和流式细胞术检测细胞凋亡率来评估新生大鼠心肌细胞损伤程度。 结果与结论：模型组乳酸脱氢酶活性明显高于其余各组(P < 0.01),同时骨髓间充质干细胞条件培养液+抑制剂组也高于骨髓间充质干细胞条件培养液组(P < 0.01);骨髓间充质干细胞条件培养液组细胞凋亡率低于与骨髓间充质干细胞条件培养液+抑制剂组(P < 0.01),并且都低于与模型组(P < 0.01)。证明了骨髓间充质干细胞条件培养液抑制了过氧化氢诱导的新生大鼠心肌细胞凋亡,该作用部分是通过PI3K途径发挥的。 关键词：心肌细胞;骨髓间充质干细胞;细胞凋亡;缺血再灌注;过氧化氢     

骨髓间充质干细胞膜微粒促进大鼠心肌梗死后血管新生

目的:观察骨髓间充质干细胞膜微粒(MSC-MPs)对大鼠心肌梗死后血管新生以及心功能的影响。方法:提取Sprague-Dawley大鼠MSCs并培养,在低氧低营养条件下培养72 h,以诱导细胞凋亡释放MSC-MPs。将培养上清液超速离心获取MSC-MPs,透射电镜下观察其大小及形态,并用流式细胞术分析其表型。建立SD大鼠心肌梗死模型,心肌梗死边缘区注射膜微粒及对照试剂。超声心动图检测心功能,Masson染色检测心梗面积,免疫组织化学染色技术检测梗死边缘区血管α-平滑肌肌动蛋白和von Willebrand因子以确定血管新生情况,real-time PCR检测心梗组织中血管内皮生长因子(VEGF)表达变化。结果:MSCs凋亡后可以释放膜微粒,MSC-MPs来自MSCs,直径为100~1 000 nm。心肌梗死大鼠心肌内注射MSC-MPs后,第7天和第28天时心功能明显改善,第28 d时心梗面积比对照组减小,新生血管密度明显增加,第7天时心梗组织VEGF的表达增加。结论:MSC-MPs可以促进大鼠心肌梗死后的血管新生,改善心功能。     

外周血间充质干细胞移植心肌梗死兔新生血管及心功能的变化

背景：药物治疗和支架置入治疗尚不能修复心肌梗死后已坏死的心肌。 目的：观察外周血间充质干细胞移植治疗对心肌梗死兔新生血管及心功能的影响。 方法：随机抽签法将36只大白兔分为假手术组,间充质干细胞移植组和对照组,结扎兔冠状动脉左室支建立心肌梗死模型。 结果与结论：移植后4周,流式细胞仪分析显示绝大部分间充质干细胞表达CD44,极少量细胞表达CD34和CD45。间充质干细胞移植组梗死心肌组织有移植的间充质干细胞存活,超声心动仪示间充质干细胞移植组左心室射血分数及短轴缩短率明显高于对照组(P < 0.01);左心室收缩末内径和舒张末内径明显小于对照组(P < 0.01)。间充质干细胞移植组心肌纤维化程度、心肌梗死面积均明显小于对照组(P < 0.01)。免疫组织化学染色显示间充质干细胞移植组新生毛细血管密度明显高于对照组(P < 0.01)。提示外周血间充质干细胞移植增加了梗死心肌新生血管密度,改善心脏的功能。     

糖尿病与正常大鼠骨髓间充质干细胞移植治疗心肌梗死的比较

背景：目前国内外在干细胞移植治疗心肌梗死的研究中,大多采用正常或者年轻的骨髓间充质干细胞作为移植细胞来源。 目的：比较糖尿病和正常大鼠骨髓间充质干细胞移植治疗心肌梗死的疗效差别。 方法：无菌条件下获取正常大鼠及糖尿病大鼠的骨髓间充质干细胞,建立大鼠心肌梗死模型并随机分为3组,分别于心肌梗死病灶区注射100 μL含有105-106个F2代正常大鼠或糖尿病大鼠来源骨髓间充质干细胞的细胞混悬液,空白对照组注射100 μL含体积分数20%胎牛血清的DMEM。移植后1个月行苏木精-伊红染色检测各组梗死区域心肌组织形态的变化;通过免疫组化方法检测Bcl-2的表达。 结果与结论：通过对细胞形态观察及流式细胞术鉴定,大鼠股骨骨髓贴壁培养可获取纯度较高的骨髓间充质干细胞,绘制细胞生长曲线结果显示正常大鼠骨髓间充质干细胞较糖尿病大鼠骨髓间充质干细胞生长快。移植后1个月,正常大鼠干细胞移植组梗死区域心肌组织形态较糖尿病大鼠干细胞移植组及空白对照组明显改善,梗死区域心肌组织Bcl-2的表达也高于其他2组。证实正常大鼠来源骨髓间充质干细胞较糖尿病大鼠骨髓间充质干细胞生长明显加快,且糖尿病使骨髓干细胞移植治疗心肌梗死的疗效降低。     

血红素氧合酶-1修饰的骨髓间充质干细胞心肌移植对梗死后心肌细胞凋亡及左心室功能的影响

目的： 探讨血红素氧合酶-1(HO-1)修饰的骨髓间充质干细胞(MSCs)对心肌梗死后心肌细胞凋亡及左心室功能的影响。方法: 取大鼠骨髓,体外分离扩增培养MSCs,HO-1腺病毒转染。结扎左前降支1 h后,分别将HO-1-MSCs、MSCs多点注射到大鼠心脏梗死区周边,对照组注射等量PBS。移植后第4 d,Western blotting检测梗死区周边HO-1蛋白、促凋亡蛋白Bax的表达;ELISA检测梗死区周边组织细胞因子血管内皮生长因子(VEGF)、b-成纤维生长因子(bFGF)的表达,第7 d超声心动图检测各组大鼠心功能变化。4周后,取梗死区周边心肌行Masson染色和免疫组化CD34因子染色。结果: Adv-HO-1转染MSCs后获稳定表达;HO-1蛋白在HO-1-MSCs组的表达明显高于MSCs组和对照组(P<0.01);促凋亡蛋白Bax的表达明显低于其它2组(P<0.01);细胞因子VEGF、bFGF的表达不同程度地高于其它2组(P<0.01)。HO-1-MSCs组左室收缩功能各项指标明显优于其它2组(P<0.01)。移植4周后,HO-1-MSCs组梗死区周边毛细血管密度明显高于MSCs组和对照组(P<0.01),HO-1-MSCs组心室壁变厚,心室腔明显缩小,胶原蛋白沉积减少。结论: HO-1修饰的MSCs分泌细胞因子协同HO-1蛋白抑制心肌细胞凋亡,促血管新生,抑制心室重构,改善心功能。     

干细胞生长因子和粒细胞集落刺激因子与心肌梗死大鼠体内骨髓间充质干细胞的迁移

背景：外周静脉移植间充质干细胞只有1%~5%的移植细胞能归巢到心肌梗死区域。 目的：观察干细胞生长因子、粒细胞集落刺激因子对骨髓间充质干细胞归巢的影响。 方法：采用贴壁培养法分离培养SD大鼠骨髓间充质干细胞,取传至3~5代细胞。建立SD大鼠急性心肌梗死模型,干细胞生长因子组、粒细胞集落刺激因子组、干细胞生长因子+粒细胞集落刺激因子组在骨髓间充质干细胞移植前3 d和移植后3 d单独或混合皮下注射干细胞生长因子、粒细胞集落刺激因子,骨髓间充质干细胞组不注射细胞因子。 结果与结论：荧光显微镜下观察,骨髓间充质干细胞迁移至心肌梗死组织,骨髓间充质干细胞组、干细胞生长因子组、粒细胞集落刺激因子组迁移至心肌梗死区的骨髓间充质干细胞数量没有明显的区别(P > 0.05),干细胞生长因子+粒细胞集落刺激因子组的骨髓间充质干细胞数量明显高于其他3组(P < 0.05)。免疫荧光组织化学显示,植入的部分骨髓间充质干细胞表达心肌特异蛋白cTnI。结果说明干细胞生长因子和粒细胞集落刺激因子两种细胞因子联合应用可以促进骨髓间充质干细胞归巢至心肌梗死区域,在体内微环境的诱导下,骨髓间充质干细胞能够转化为心肌样细胞。     

同种异体骨髓间充质干细胞移植上调急性心肌梗死大鼠Cx43的表达

目的研究同种异体骨髓间充质干细胞(MSCs)移植心肌梗死(MI)大鼠后缝隙连接蛋白43(Cx43)在不同时期的动态变化。方法建立大鼠MI模型。将同种异体MSCs用5-氮胞苷诱导成心肌样细胞并行荧光标记,经二次开胸注射入MI大鼠梗死区和梗死边缘区。各亚组分别于移植后4、8和12周在荧光显微镜下跟踪MSCs移植情况。同时用免疫组化分析Cx43表达与缝隙连接(GJ)分布。结果MSCs体外诱导可分化为自发搏动的心肌样细胞,表达心肌特异性肌钙蛋白T(cTnT)和形成肌丝结构。MSCs移植后可长期存活并在4、8和12周,并有效上调缺血区Cx43的表达,改善GJ分布紊乱状态。在梗死区Cx43无特殊改变。结论MSCs具有分化为心肌样细胞的可塑性,移植后上调MI后缺血区Cx43表达,改善GJ分布紊乱。     

MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine

Mesenchymal stem cells (MSCs) have attracted much attention in regenerative medicine owing to their apparent usefulness as multi-potent replacement cells. The potential of MSC therapy can be further improved by transforming MSCs with therapeutic genes that maximize the efficacy of gene therapy and their own therapeutic ability. Since most conventional transfection methodologies have shown marginal success in delivering exogenous genes into primary cultured cells, efficient gene transfer into primary MSCs is a prerequisite for the development of MSC-based gene therapy strategies to achieve repair and regeneration of damaged tissues. Herein, facially amphipathic bile acid-modified polyethyleneimine (BA-PEI) conjugates were synthesized and used to transfer hypoxia-inducible vascular endothelial growth factor gene (pHI-VEGF) in MSCs for the treatment of rat myocardial infarction. Under the optimized transfection conditions, the BA-PEI conjugates significantly increased the VEGF protein expression levels in rat MSCs, compared with traditional transfection methods such as Lipofectamine™ and branched-PEI (25 kDa). Furthermore, the prepared pHI-VEGF-engineered MSCs (VEGF-MSCs) resulted in improved cell viability, particularly during severe hypoxic exposure in vitro. The transplantation of MSCs genetically modified to overexpress VEGF by BA-PEI enhanced the capillary formation in the infarction region and eventually attenuated left ventricular remodeling after myocardial infarction in rats. This study demonstrates the applicability of the BA-PEI conjugates for the efficient transfection of therapeutic genes into MSCs and the feasibility of using the genetically engineered MSCs in regenerative medicine for myocardial infarction.     

Intravenously Injected Mesenchymal Stem Cells Home to Infarcted Myocardium Without Altering Cardiac Function

Background： Systemic delivery of mesenchymal stem cells （MSCs） to the infarcted myocardium is an attractive noninvasive strategy, but therapeutic effect of this strategy remain highly controversial. Methods： Myocardial infarction was induced in female Sprague-Dawley rats by transient ligation of the left anterior descending coronary artery for 60 min. Either 2.5 × 106 DiI-labeled MSCs or equivalent saline was injected into the tail vein at 24 h after infarction. Results： Three days later, MSCs localized predominantly in the infarct region of heart rather than in the remote region. MSCs were also observed in spleen, lung and liver. At 4 weeks after infarction, echocardiographic parameters, including ejection fraction, fractional shortening, left ventricular end-diastolic and end-systolic diameters, were not significantly different between MSCs and saline groups. Hemodynamic examination showed that ± dp/dtmax were similar between MSCs and saline-treated animals. Histological evaluation revealed that infarct size and vessel density were not significantly changed by MSCs infusion. Conclusion： Intravenously injected MSCs can home to infarcted myocardium, but plays a limited role in cardiac repair following myocardial infarction.     

Impact of myocardial infarct proteins and oscillating pressure on the differentiation of mesenchymal stem cells: effect of acute myocardial infarction on stem cell differentiation

Stem cell transplantation in acute myocardial infarction (AMI) has emerged as a promising therapeutic option. We evaluated the impact of AMI on mesenchymal stem cell (MSC) differentiation into cardiomyocyte lineage. Cord blood-derived human MSCs were exposed to in vitro conditions simulating in vivo environments of the beating heart with acute ischemia, as follows: (a) myocardial proteins or serum obtained from sham-operated rats, and (b) myocardial proteins or serum from AMI rats, with or without application of oscillating pressure. Expression of cardiac-specific markers on MSCs was greatly induced by the infarcted myocardial proteins, compared with the normal proteins. It was also induced by application of oscillating pressure to MSCs. Treatment of MSCs with infarcted myocardial proteins and oscillating pressure greatly augmented expression of cardiac-specific genes. Such expression was blocked by inhibitor of transforming growth factor beta(1) (TGF-beta(1)) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocyte-specific markers were able to make a coupling with cardiomyocytes but not to selfbeat. The pathophysiologic significance of in vitro results was confirmed using the rat AMI model. The protein amount of TGF-beta(1) and BMP-2 in myocardium of AMI was significantly higher than that in normal myocardium. When MSCs were transplanted to the heart and analyzed 8 weeks later, they expressed cardiomyocyte-specific markers, leading to improved cardiac function. These in vitro and in vivo results suggest that infarct-related biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-beta/BMP-2 pathways.     

Monocyte chemotactic protein 1 increases homing of mesenchymal stem cell to injured myocardium and neovascularization following myocardial infarction

Objective:To investigate the effect of MCP-1 on mesenchymal stem cells(MSCs) homing to injured myocardium in a rat myocardial infarction(MI) model. Methods:Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein 1(MCP-1) expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1,2, 4,7,14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 106 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results:Self-generating MCP-1 expression was increased at the first day, peaked at the 7th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-Mi group(P = 0.000), the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups (P = 0.000). Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups(P= 0.000). Neovascularization in MCP-1 injected group significantly increased compared with that of other groups(P = 0.000). Conclusion: Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.     

血红素氧合酶-1对移植入急性梗死区心肌骨髓间充质干细胞的保护作用

目的:观察血红素氧合酶-1(HO-1)体内外对缺血环境下骨髓间充质干细胞(MSCs)的保护作用及梗死后心脏血流动力学的影响。方法:取大鼠骨髓,体外分离扩增培养MSCs;HO-1腺病毒转染MSCs,荧光显微镜下观察绿色荧光蛋白(GFP)的表达;流式细胞仪检测无氧无血清条件培养的HO-1-MSCs、MSCs的凋亡率。建立心梗模型,分别将DAPI-HO-1-MSCs、DAPI-MSCs多点注射到大鼠心脏梗死区周边,对照组注射等量PBS,比较各组MSCs存活率;4周后测定血流动力学指标。结果:HO-1转染的MSCs可稳定高效地表达GFP;在无氧无血清条件下,HO-1-MSCs的凋亡率显著低于MSCs(P<0.01);细胞移植到梗死后心肌,HO-1-MSCs组存活MSCs计数在第7天明显高于MSCs组(P<0.05),且血流动力学各项指标较MSCs组明显改善(P<0.05)。结论:HO-1可在体内、体外实验中提高缺血环境下MSCs的存活率,并改善心肌梗死后血流动力学和心功能,为优化干细胞治疗提供了新思路。