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。     

毛囊培养上清液诱导大鼠骨髓间充质干细胞分化的研究

目的探讨毛囊培养上清液诱导体外培养的大鼠骨髓间充质干细胞(MSCs)向毛囊干细胞横向分化的潜能。方法采用完全贴壁法分离培养大鼠MSCs,取第3代MSCs,用免疫细胞化学染色技术鉴定CD44和CD29。用毛囊培养上清液为条件培养液诱导MSCs,倒置相差显微镜观察细胞形态学变化,对诱导后的细胞进行角蛋白15的免疫细胞化学染色和免疫荧光细胞化学染色,逆转录-聚合酶链反应(RT-PCR)进一步鉴定诱导后细胞角蛋白15的表达。结果体外培养的MSCs,CD44、CD29表达阳性。经毛囊上清液诱导后,免疫细胞化学、免疫荧光细胞化学染色鉴定,部分细胞角蛋白15表达阳性;同时RT-PCR也检测到keratin 15 mRNA的表达。结论体外培养的骨髓间充质干细胞经毛囊培养上清液诱导可以分化为毛囊干细胞样的细胞。     

心肌微环境与5-氮杂胞苷诱导脂肪间充质干细胞心肌分化的差异（英文）

目的探讨体内心肌微环境及体外5-氮杂胞苷(5-aza)诱导脂肪间充质干细胞分化为心肌样细胞的作用差异。方法取小鼠腹股沟的皮下脂肪组织,分离培养脂肪间充质干细胞(ADMSCs),对其进行表面标记和成骨、成脂分化能力鉴定。选取生长状态良好的第3代ADMSCs,分为5-aza体外诱导组、体内心肌移植组,体外诱导3周以及体内移植1周后,采用免疫荧光技术检测特异性心肌肌钙蛋白T(cT nT)的表达。结果两种诱导方法ADMSCs均表达cT nT,5-aza诱导组3周表达率(33.33±3.79)%,移植组1周表达率(42.93±4.04)%,移植组1周较5-aza诱导组3周具有更高的分化效率(P0.05)。结论体外5-aza化学诱导和体内心肌微环境均可使ADMSCs分化为心肌样细胞,但心肌微环境的诱导分化效率明显高于5-aza的作用。     

胚胎干细胞联合碱性成纤维细胞生长因子移植对大鼠急性心肌梗死的影响

目的 探讨胚胎干细胞-D3株(ES-D3)联合碱性成纤维细胞生长因子(bFGF)移植治疗大鼠急性心肌梗死,是否有利于心脏结构的恢复和心功能的改善.方法 Wistar大鼠40只随机均分成5组,分别为正常对照组(组1)、梗死未治疗组(组2)、培养基注射组(组3)、ES-D3移植组(组4)、ES-D3 bFGF移植组(组5).大鼠急性心肌梗死造模后1周移植体外分化并经标记的ES-D3,4周后进行心功能及组织学检测.结果 ES-D3体外能分化为心肌样细胞.梗死后4周检测表明,移植细胞在大鼠体内稳定存活.心功能及组织学检测表明,组2与组3大鼠无显著差异(P>0.05).与组2比较,组4和组5大鼠心肌梗死面积均显著减小,左心室重量减轻(P<0.01);毛细血管密度显著增高(P<0.01);左心室功能显著改善.结论 急性心肌梗死后移植ES-D3可以促进大鼠心血管新生、阻止心室重构、减少瘢痕面积、显著改善心功能,联合应用bFGF可进一步获益.     

兔骨髓间充质干细胞来源的心肌(样)细胞的诱导分化研究

目的体外诱导骨髓间充质干细胞(Mesenchymal stem cells,MSCs)向肌源性细胞分化,探索诱导后的MSCs移植于心肌梗死区的存活和分化情况。方法提取、分离、培养兔的MSCs。经5-氮胞苷诱导后,进行免疫组化,电镜观察。4',6二乙酞基-2-苯基吲哚(DAPI)标记MSCs,建立兔心肌梗死模型。实验动物随机分两组:实验组(n=10)在心梗区域注入经诱导后的MSCs;对照组(n=10)在心梗区域注入不含MSCs的培养液。移植4周后,进行病理标本观察和免疫组化检测。结果5-氮胞苷诱导MSCs4周,部分细胞表达肌钙蛋白T(troponin T),电镜观察到肌丝形成。MSCs在体外用DAPI标记,用荧光显微镜观察细胞发蓝色荧光。移植4周后,在实验组中用荧光显微镜观察可见梗死区组织标本中可见DAPI标记带蓝色荧光的供体细胞核,移植细胞表达troponin T。结论MSCs经5-氮胞苷诱导后可向心肌细胞转化。移植细胞可在心肌存活,并向心肌细胞(样)转化。     

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：     

心肌微环境与5-氮杂胞苷诱导脂肪间充质干细胞心肌分化的差异

目的 探讨体内心肌微环境及体外5-氮杂胞苷（5-aza）诱导脂肪间充质干细胞分化为心肌样细胞的作用差异。 方法 取小鼠腹股沟的皮下脂肪组织,分离培养脂肪间充质干细胞（ADMSCs）,对其进行表面标记和成骨、成脂分化能力鉴定。选取生长状态良好的第3代ADMSCs,分为5-aza体外诱导组、体内心肌移植组,体外诱导3周以及体内移植1周后,采用免疫荧光技术检测特异性心肌肌钙蛋白T（cTnT）的表达。 结果 两种诱导方法ADMSCs均表达cTnT,5-aza诱导组3周表达率（33.33±3.79）%,移植组1周表达率（42.93±4.04）%,移植组1周较5-aza诱导组3周具有更高的分化效率（P<0.05）。 结论 体外5-aza化学诱导和体内心肌微环境均可使ADMSCs分化为心肌样细胞,但心肌微环境的诱导分化效率明显高于5-aza的作用。     

大鼠骨髓间充质干细胞体外诱导分化为心肌样细胞

目的 采用骨髓间充质干细胞(MSCs)体外诱导为心肌样细胞,为干细胞移植治疗心衰提供一种新的细胞材料.方法 取SD大鼠四肢骨骨髓,分离培养MSCs,分别用终浓度为5、10、15、20 μmol/L的5-氮胞苷(5-aza)定向诱导,相差显微镜观察细胞形态学变化,应用免疫细胞化学、激光扫描共焦显微镜技术检测结蛋白(desmin),α-横纹肌肌动蛋白(α-sarcomeric actin)、心肌特异性肌钙蛋白(C-TnT)的表达,透射电镜鉴定.在诱导后7d、21 d和28 d,3个时间点以半定量RT-PCR方法检测细胞心肌早期转录因子GATA4和心肌特异性肌凝蛋白重链αMHC的表达.结果 MSCs体外经5-aza诱导后分化的细胞desmin、α-sarcomericactin、C-TnT均表达阳性,5 μmol/L组阳性表达较高,透射电镜下可见到平行排列的肌丝.RT-PCR结果显示,GATA4于诱导后7 d弱表达,21 d表达增强,28 d表达减弱.αMHC在诱导后7 d不表达,21 d弱表达,28 d表达明显.结论 骨髓间充质干细胞能够在体外被诱导分化为心肌样细胞,是自体心肌细胞一种良好的供体来源.     

5-氮杂胞苷诱导人脐带间充质干细胞向心肌样细胞的分化

背景：5-氮杂胞苷能诱导人脐带间充质干细胞分化为心肌细胞。 目的：以5-氮杂胞苷诱导人脐带间充质干细胞分化为心肌细胞。 方法：采用贴壁培养法分离、纯化人脐带间充质干细胞,以5-氮杂胞苷诱导第3代人脐带间充质干细胞分化为心肌样细胞。 结果与结论：诱导前人脐带间充质干细胞呈典型的梭形;诱导后一二周细胞体积变大,三四周后相邻细胞间胞膜有接触,逐渐相连呈肌管状,细胞胞质内可见细丝样结构。诱导4周后免疫组织化学鉴定人脐带间充质干细胞cTnI表达阳性,未诱导细胞cTnI表达阴性;诱导组Nkx2.5、GATA 4 mRNA表达水平较未诱导组显著增加(P < 0.05)。提示5-氮杂胞苷可能通过调控GATA4、Nkx2.5基因的表达促进人脐带间充质干细胞分化为心肌样细胞,并促进其成熟。     

骨髓间充质干细胞分化为心肌样细胞的实验研究

目的通过体外诱导研究大鼠骨髓间充质干细胞向心肌样细胞的分化,为心衰的干细胞移植治疗提供实验依据。方法分离培养大鼠骨髓间充质干细胞,采用5-氮杂胞苷定向诱导,通过形态学、免疫细胞化学及磷钨酸苏木素染色(PTAH)鉴定。结果诱导后细胞以梭形、柱状为主;部分细胞有分支,核一个、卵圆形、居中,类似心肌细胞形态;诱导24h后培养2周,Sarcomeric Actin和Connexin-43表达较弱,以后表达逐渐增强;诱导细胞PTAH阳性。结论骨髓间充质干细胞能在体外被诱导分化为心肌样细胞,有望成为心衰时干细胞移植治疗的理想细胞材料。     

人脐带干细胞移植在心肌梗死大鼠心肌内的迁移、分化及对心脏功能的影响

目的 探讨脐带干细胞移植对大鼠心肌梗死后心脏功能的影响及细胞在心肌内的迁移和分化。方法 2010年10月—2011年6月收集南京鼓楼医院妇产科10例健康胎儿脐带,采用胶原酶胰酶消化法分离脐带干细胞。选取8周龄、体质量260～280 g 的SD雄性大鼠30只,采用结扎大鼠冠状动脉前降支建立心肌梗死模型。造模后第14天行心脏超声检查,将造模成功的大鼠随机分为移植组(12只)和对照组(11只),并分别经心肌每只大鼠注射200 μl人脐带干细胞悬液和PBS。在细胞移植前和移植后第14、28天行心脏超声心动图检查,测定心脏功能。在移植后28天,处死移植组大鼠,制作心脏冷冻切片。切片采用血管特异性平滑肌动蛋白α(α-SMA)抗体、内皮特异性血管性血友病因子(vWF) 抗体及心肌特异性肌钙蛋白T (cTnT)抗体染色,在荧光显微镜下观察脐带干细胞的存活、迁移情况,以及血管平滑肌细胞、血管内皮细胞和心肌细胞的分化情况。结果 30只大鼠中造模成功23只,脐带干细胞移植后存活20只,其中移植组10只,对照组10只。超声心动检查,与移植前比较,两组大鼠干细胞移植后第14、28天的左室射血分数、短轴缩短率均有明显增加,差异均有统计学意义(t_射血分数=3.864、3.690,t_{短轴缩短率}=6.397、5.904,P值均<0.05)。移植后组间比较:干细胞移植后第14天,两组大鼠的左心室射血分数差异无统计学意义(P＞0.05),而左室短轴缩短率移植组大于对照组,差异有统计学意义(t=2.771,P<0.05);干细胞移植后第28天,移植组大鼠的左室射血分数和短轴缩短率均明显高于对照组,差异均有统计学意义(t=2.977、2.140,P值均<0.05)。荧光显微镜下观察,移植组可见脐带干细胞能够在梗死心肌内存活并发生迁移,α-SMA抗体、vWF抗体和cTnT抗体染色显示移植的脐带干细胞能够分化为血管平滑肌细胞、内皮细胞和心肌细胞。结论 脐带干细胞能够在梗死心肌内迁移,在局部梗死心肌微环境下,能够分化为血管平滑肌细胞、内皮细胞和心肌细胞,促进血管新生和心肌再生,从而促进心脏功能的恢复。     

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.     

Immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells

Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73⁺, CD90⁺, CD105⁺, and CD34⁻, CD45⁻, HLA-DR⁻) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8⁺ T cells markedly decreased and CD4⁺ T cells changed lightly. Moreover, the infusion of UC-MSCs in recipient mice transplanted with donor bone marrow cells ameliorated acute graft-versus host disease (aGVHD) and extended survival. In conclusion, UC-MSCs might negatively modulate immunoreactions, and have application potential in the treatment of aGVHD caused by allogeneic stem cells transplantation.     

不同月龄人脐带间充质干细胞移植梗死心肌的血运重建

背景：干细胞移植有利于心肌梗死后的心肌血运重建及改善心功能,HLA-G分子在免疫耐受状态的形成及维持中具有重要作用。 目的：观察不同月龄有HLA-G表达差异的人脐带间充质干细胞移植后对急性心肌梗死兔血运重建的影响。 方法：健康新西兰大白兔30只,随机数字表法分为小月龄细胞移植组、足月龄细胞移植组及对照组。建立兔心肌梗死模型后2周,将小月龄人脐带间充质干细胞和足月人脐带间充质干细胞分别标记BrdU,多点注射心肌梗死的交界区和中心区,对照组注射无血清培养基。 结果与结论：移植后4周,小月龄和足月龄细胞移植组在心肌梗死区均发现有BrdU示踪细胞,且两组梗死区心肌纤维化程度、心肌梗死面积均少于对照组(P < 0.01),两移植组间差异也有显著性意义(P < 0.05)。Ⅷ因子染色见小月龄细胞移植组毛细血管密度高于足月龄细胞移植组(P < 0.01),且两移植组与对照组比较差异也有显著性意义(P < 0.05)。提示HLA-G表达量较高的小月龄脐带间充质干细胞能更好促进梗死区血管新生,改善血运重建,有潜力成为心肌细胞移植的更理想来源。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：     

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。     

骨髓间充质干细胞移植心肌梗死大鼠的心功能

背景：前期研究发现移植的骨髓间充质干细胞能在受损心肌组织内存活和分化。 目的：进一步观察局部注射移植同种异体骨髓间充质干细胞对心肌梗死模型大鼠心功能的影响。 方法：体外培养的同种异体骨髓间充质干细胞达到一定数量(10⁶)后用BrdU标记。24只SD大鼠随机分为3组：正常对照组未行冠状动脉前降支结扎,取骨髓间充质干细胞约1 mL直接注射到冠状动脉前降支心肌的周围;假移植组：在冠状动脉前降支结扎后7 d,取等量DMEM培养液直接注射到梗死心肌的周围;骨髓间充质干细胞移植组：冠状动脉前降支结扎后7 d,取等量骨髓间充质干细胞直接注射到梗死心肌的周围;分别于移植前、移植后5周测定大鼠心功能。 结果与结论：①移植后5周假移植组最大左室收缩末压、左室内压最大(最小)变化速率均低于移植前(P < 0.01),而左室舒张末压高于移植前(P < 0.01);移植后5周骨髓间充质干细胞移植组最大左室收缩末压、左室内压最大(最小)变化速率高于移植前(P < 0.01),而左室舒张末压低于移植前(P < 0.01)。②移植后5周,骨髓间充质干细胞移植组大鼠的最大左室收缩末压、左室内压最大(最小)变化速率均高于假移植组(P < 0.01),而左室舒张末压明显低于假移植组(P < 0.01)。结果可见骨髓间充质干细胞移植可明显改善心肌梗死模型大鼠心功能。     

乌司他丁联合脐带间充质干细胞移植脊髓损伤大鼠后肢运动功能和 运动诱发电位的变化

背景：乌司他丁能减轻炎性反应、清除氧自由基,对中枢神经系统损伤具有保护作用,能有效地提高脊髓损伤后移植细胞的存活率。 目的：观察乌司他丁联合脐带间充质干细胞移植对脊髓损伤大鼠后肢功能的影响。 方法：Wistar大鼠建立脊髓损伤动物模型后随机分成4组：空白对照组尾静脉注射培养液+腹腔注射生理盐水,细胞移植组尾静脉注射脐带间充质干细胞,乌司他丁组腹腔注入乌司他丁,联合组尾静脉注射脐带间充质干细胞,同时腹腔注入乌司他丁。 结果与结论：移植4周后联合组下肢运动功能优于细胞移植组和乌司他丁组(P < 0.05),细胞移植组和乌司他丁组优于空白对照组(P < 0.05)。移植后4周,PKH26标记的阳性细胞数联合移植组多于细胞移植组,细胞移植组多于乌司他丁组和空白对照组(P < 0.01)。移植后8周,联合组大鼠体感诱发电位及运动诱发电位的潜伏期、波幅明显优于其他3组(P < 0.05或P < 0.01)。提示乌司他丁联合应用脐带间充质干细胞移植可促进脊髓损伤大鼠神经突触的再生,改善其肢体运动功能和电生理功能,其效果优于单独应用乌司他丁或脐带间充质干细胞。     

静脉移植骨髓间充质干细胞对心肌病心力衰竭心功能的影响

BACKGROUND:Bone marrow mesenchymal stem cell transplantation can effectively improve decreased cardiac function caused by heart failure, but there is a lack of research about the effect in bone marrow mesenchymal stem cell transplantation on cardiac function in heart failure induced by cardiomyopathies. OBJECTIVE:To explore the effect of bone marrow mesenchymal stem cell transplantation on cardiac function in patients with cardiomyopathies accompanied by heart failure. METHODS:Totally 40 Sprague-Dawley rats were enrolled, and bone marrow mesenchymal stem cells were isolated from 10 rats, and the remaining rats were equivalently randomized into normal, model and stem cell transplantation groups. Then rats in the model and stem cell transplantation groups were given intraperitoneal injection of hydrochloric acid doxorubicin to prepare cardiomyopathy-induced heart failure models. At 7 days after modeling, the stem cell transplantation group was treated with bone marrow mesenchymal stem cells through intravenous transplantation, and the model group was treated with equal amount of DMEM medium. Four weeks later, cardiac function of each rat was detected, and the cell survival and differentiation were observed by immunofluorescence method. RESULTS AND CONCLUSION:At 4 weeks after transplantation, compared with normal and stem cell transplantation groups, the left ventricular systolic pressure and maximum rise/fall rate of left ventricular pressure were significantly decreased, but the left ventricular end diastolic pressure significantly increased in the model group (P < 0.05). And there was no significant difference between the normal group and the stem cell transplantation group (P > 0.05). High and dense fluorescence intensity was observed in the host myocardium immediately after transplantation. Subsequently, the fluorescence intensity and density decreased at 4 weeks, but the cell migration could be found, and some cells expressed cardiac troponin T. These results show that intravenous transplantation of bone marrow mesenchymal stem cells can improve cardiac function in rats with heart failure due to cardiomyopathies. Besides, the transplanted cells can survive in the host, and differentiate into cardiomyocyte-like cells.     

骨髓干细胞动员与移植治疗心肌梗死的比较

目的：比较骨髓干细胞动员与骨髓单个核细胞移植对兔心肌梗死的治疗作用，探讨更有效、更适用的干细胞治疗心肌梗死的方法。 方法： 将30只新西兰兔采用结扎前降支的方法复制心肌梗死模型，随机分为动员组、移植组和对照组，动员组（n=10）心梗后3 h开始皮下注射粒细胞集落刺激因子（G-CSF）30 μg·kg-1·d-1，连续使用5 d，第5 d抽取静脉血约10 mL，分离单个核细胞(BMCs)用5-溴脱氧尿嘧啶核苷（BrdU）标记后，经静脉注入动物体内。移植组（n=10）心梗后7-10 d，抽取骨髓3-5 mL,分离MNCs用BrdU标记，然后开胸将细胞移植至梗死区，对照组（n=10）不采取任何治疗措施。心梗后1周及5周采用超声心动图（UCG）检查心脏功能变化，5周时作血液动力学测定，取心脏作免疫组织化学鉴定。 结果： 心梗后5周，动员组左室射血分数（EF）明显高于1周时，移植组无变化，对照组显著下降。5周时动员组及移植组左室舒张末压（LVEDP）、+dp/dtmax和-dp/dtmax与对照组相比均有显著差异。动员组及移植组在心肌梗死区均发现有BrdU标记的阳性细胞，两组梗塞区血管密度明显高于对照组，但均未发现有新生的平滑肌细胞及心肌细胞。 结论： 骨髓干细胞动员及BMCs移植治疗心肌梗死，均能通过促进梗死区血管新生，明显改善心脏功能，骨髓干细胞动员可能为心肌梗死的治疗提供一种新的无创性手段。     

不同孕周人脐带间充质干细胞移植改善心肌梗死模型心脏功能的比较

BACKGROUND: Stem cells have multi-directional differentiation and self-replication abilities, under certain conditions, which can differentiate into myocardial cells to repair the damaged myocardium. OBJECTIVE: To investigate the effects of transplantation of umbilical cord mesenchymal stem cells derived at different gestational weeks on infarct size and angiogenesis in the infarct region of experimental rabbits with myocardial infarction. METHODS: Ten full-term umbilical cord samples and 10 umbilical cord samples of aborted fetuses at 10-12 gestation weeks were selected to in vitro isolate umbilical cord mesenchymal stem cells that were subjected to BrdU labeling. HLA-G expression was detected in the cells. Thirty white rabbits were selected to make myocardial infarction models, and 2 weeks after modeling, the model rabbits were randomized into aborted cell transplantation group, full-term cell transplantation group and control group (n=10 per group). Then, BrdU-labeled cells were injected correspondingly into the infarct region of rabbits in the two cell transplantation groups. Rabbits in the control group were subjected to an equal volume of serum-free. Four weeks after transplantation, heart function of rabbits was monitored using electrocardiogram, and myocardial tissues were taken to measure infarct size and blood capillary density. RESULTS AND CONCLUSION: HLA-G expression was different in different sources of umbilical cord mesenchymal stem cells: high HLA-G expression was found in the aborted umbilical cord mesenchymal stem cells, and meanwhile, low HLA-G expression was found in the full-term umbilical cord mesenchymal stem cells. Compared with the control group, the left ventricular end-diastolic volume and left ventricular ejection fraction of aborted and full-term cell transplantation groups were significantly improved, especially in the aborted cell transplantation group (P < 0.05). BrdU-positive cells were found in the infarct site in both transplantation groups. Compared with the control group, the infarct size and capillary density were improved most significantly in the aborted cell transplantation group followed by the full-term cell transplantation group (P < 0.05). Electrocardiogram findings showed significant improvement in both cell transplantation groups compared with the control group (P < 0.05), especially in the aborted cell transplantation group. These findings indicate that umbilical cord mesenchymal stem cells derived at low gestational weeks improve the heart function more significantly than the full-term umbilical cord mesenchymal stem cells, which have the potential to become a better source of cardiomyocytes for transplantation.