骨髓间充质干细胞治疗大鼠急性心肌梗死

目的:比较经不同途径移植骨髓间充质干细胞(BMSCs)治疗大鼠急性心肌梗死(AMI)的疗效,探求更为适合的移植途径。方法:采集大鼠BMSCs,并进行培养及鉴定。以5-氮胞苷(5-aza)10μmol/L,诱导BMSCs为心肌样细胞并鉴定。建立大鼠急性心肌梗死模型并鉴定。对照组不予处理,静脉移植组和心外膜移植组分别经尾静脉和心外膜移植心肌样细胞悬液200μl(心肌样细胞5×10~6),联合移植组同时经尾静脉和心外膜分别移植心肌样细胞悬液各200μl。4周后观察SD大鼠心肌组织形态及蛋白表达情况。结果:静脉移植组、心外膜移植组、联合移植组的心肌梗死区域均可见有DAPI标记阳性的移植细胞,其中联合移植组较静脉移植组、心外膜移植组数量明显增多;H-E染色可见后三组较对照组梗死区域心肌细胞排列整齐,细胞核较完整,联合移植组梗死改善程度明显;后三组较对照组血管紧张素转换酶2(ACE2)表达水平升高,联合移植组较静脉移植组、心外膜移植组升高水平更显著。结论:经静脉、心外膜和两者联合移植诱导后的BMSCs均能促进梗死部位的组织修复,抑制心室重构,其中联合移植途径治疗效果更明显。     

大鼠骨髓间充质干细胞移植治疗心肌梗死的实验研究

目的　研究骨髓间充质干细胞(BMSCs)移植对心肌梗死大鼠左心功能的影响以及在心肌病大鼠体内存活、分化的情况。 方法　结扎左冠状动脉前降支制备大鼠心肌梗死模型,采用同种异体大鼠BMSCs 体外分离、纯化、扩增,胶体金标记。按照对BMSCs的处理方式和心肌内注射的成分不同随机分为3组:A组接受BMSCs移植治疗;B组移植经5-氮胞苷体外诱导的BMSCs;C组列为对照组,注射等量培养基;每组12只。4周后通过血流动力学各项指标评价BMSCs移植对大鼠心功能的改善情况;免疫组织化学法检测移植细胞的存活和分化。 结果 与对照组C组相比,移植组A, B两组左心功能显著改善（P<0.01）。A, B两组之间无显著性差异。移植组左心室收缩压（LVSP）、左心室等容期压力最大变化速率（±dp/dtmax）明显高于对照组（P<0.01）,左心室舒张末期压（LVEDP）明显低于对照组（P<0.01）。移植的BMSCs能在心外膜下、梗死区及与正常心肌的交界处存活并向心肌细胞分化, 心肌特异性肌钙蛋白T（cTnT）和α－横纹肌肌动蛋白（α-sarcomeric actin）表达阳性。 结论 同种异体BMSCs移植入大鼠心肌梗死区后能明显改善心功能并向心肌细胞转化。     

骨髓间充质干细胞经大鼠冠状动脉内移植的可行性

目的 研究骨髓间充质干细胞经冠状动脉内移植的安全性及可行性.方法 左侧开胸结扎SD大鼠左冠状动脉,2周后取心脏建立Langerndorff模型.将CM-DiI标记的骨髓间充质干细胞悬液注入主动脉根部,同时收集右心房回流的液体,离心后通过流式细胞仪计数细胞数量.观察是否有细胞经冠状静脉回流及数量比例.并在不同时间测LVSP、LVDP、±dp/dt、心率,评价其安全性.在体实验中取心梗后2周的大鼠,经左心室-主动脉途径将细胞悬液注射到临时阻断的主动脉根部,分别在移植后1及24 h和1及4周取材观察细胞在心脏内的位置及细胞的迁移情况.结果 离体实验发现经冠状动脉内注射骨髓间充质干细胞90%以上的细胞在心肌组织内存留,移植后LVSP、LVDP、±dp/dt、心率没有明显变化.在体内实验中发现细胞移植后早期大部分细胞分布在心外膜下心肌组织内,在心内膜下组织内较少细胞分布,而且大部分细胞在正常心肌组织内,只有少量在心梗区域.而在细胞移植后1～4周存活的细胞多在心肌梗死及交界区组织内,在正常组织内很少有移植细胞存在.结论 经冠状动脉途径进行细胞移植是安全可行的.     

骨髓间充质干细胞经大鼠冠状动脉内移植可行性研究

目的 研究骨髓间充质干细胞经冠状动脉内移植的安全性及可行性。方法 左侧开胸结扎SD大鼠左冠状动脉，2周后取心脏建立Langerndorff模型。将CM-DiI标记的骨髓间充质干细胞悬液注入主动脉根部，同时收集右心房回流的液体，离心后通过流式细胞仪计数细胞数量。观察是否有细胞经冠状静脉回流及数量比例。并在不同时间测LVSP、LVDP、±dp/dt、心率，评价其安全性。在体实验中取心梗后2周的大鼠，经左心室--主动脉途径将细胞悬液注射到临时阻断的主动脉根部，分别在移植后1及24h和1及4周取材观察细胞在心脏内的位置及细胞的迁移情况。结果 离体实验发现经冠状动脉内注射髓间充质干细胞90%以上的细胞在心肌组织内存留，移植后对LVSP、LVDP、±dp/dt、心率没有明显变化。在体内实验中发现细胞移植后早期大部分细胞分布在心外膜下心肌组织内，在心内膜下组织内较少细胞分布，而且大部分细胞在正常心肌组织内，只有少量在心梗区域。而在细胞移植后1~ 4周存活的细胞多在心肌梗死及交界区组织内，在正常组织内很少有移植细胞存在。结论 经冠状动脉内途径进行细胞移植是安全可行的。     

基底膜基质胶携带人脂肪组织来源间充质干细胞移植改善心肌梗死大鼠心脏功能

目的:应用基底膜基质胶(matrigel)携带人脂肪组织来源间充质干细胞(ADMSCs)在大鼠的心肌梗死部位注射,观察其对细胞存活的影响及改善心梗模型大鼠心脏功能的能力。方法:分离、培养、扩增人ADM-SCs,左冠状动脉前降支结扎法建立大鼠急性心肌梗死模型。将大鼠急性心肌梗死模型随机分为4组,对照组(PBS组)、matrigel组、PBS+ADMSCs组、matrigel+ADMSCs组,对移植4周后细胞的存活及心梗局部新生血管的密度进行测量,并利用心脏超声检测大鼠心脏功能。结果:与其它各组相比,matrigel+ADMSCs组的细胞4周存活细胞数量以及心肌梗死区域新生血管密度均显著提高,心脏超声结果也表明该组大鼠的心脏功能改善最为显著。结论:基底膜基质胶能够提高人脂肪组织来源间充质干细胞在大鼠心肌梗死部位的存活,有助于提高心肌梗死部位微血管生成并改善心肌梗死大鼠的心脏功能。     

透明质酸水凝胶包裹骨髓间充质干细胞改善心肌梗死大鼠的心功能(Ⅲ)

背景：作者前期的研究结果显示透明质酸水凝胶包裹骨髓间充质干细胞显著改善大鼠心肌梗死后心功能。目的：探索透明质酸水凝胶及骨髓间充质干细胞促进心肌修复的分子机制。方法：分离培养雄性SD大鼠骨髓间充质干细胞,然后用透明质酸水凝胶包裹骨髓间充质干细胞在培养皿中进行体外三维培养。结扎雌性SD大鼠左冠状动脉前降支制作心肌梗死模型,1周后行超声检测,将符合条件的大鼠随机分为4组：(1)PBS组(n=12);(2)透明质酸组(n=12);(3)骨髓间充质干细胞组(n=15);(4)骨髓间充质干细胞+透明质酸组(n=15)。造模1周后将模型鼠行二次开胸,按照分组将PBS、透明质酸水凝胶、骨髓间充质干细胞、透明质酸水凝胶包裹骨髓间充质干细胞注射到梗死边缘区及梗死区。移植后1 d、1周、2周,Western blot检测梗死区域及周边的基质金属蛋白酶2、血管内皮生长因子、胸腺素β4以及c-Kit的蛋白表达水平,移植后2周免疫荧光检测移植细胞的分化情况。结果与结论：(1)在移植后1周时,骨髓间充质干细胞组的基质金属蛋白酶2及血管内皮生长因子蛋白表达水平明显高于其他3组(P <0.05);在移植后2周时,...     

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。     

过表达IDO 大鼠骨髓间充质干细胞改善异位移植心脏存活

目的:探讨过表达IDO 大鼠骨髓间充质干细胞(BMSC)改善大鼠腹腔异位移植心脏的存活机制。方法:通过慢病毒载体GV308 携带IDO 基因转染大鼠骨髓间充质干细胞构建过表达IDO 大鼠骨髓间充质干细胞。建立大鼠腹腔异位移植心脏模型,经尾静脉给予相应细胞处理:1.利用超声心动图检测移植心脏心功能变化。于采用小动物活体成像系统评估移植心脏局部荧光强度。2.再取各组受体大鼠的脾脏,采用流式细胞技术检测CD40、CD86、CD80、MHCⅠ、CD274、CD45RA、CD45RA+CD45RB、Treg 细胞的表达情况。3.取各组移植心脏,采用HE 染色评估炎性细胞浸润情况。虞利用液相芯片检测各组血清IL-1α、IL-4、IL-1β、IL-2、IL-10、IFN-γ、IL-18、TGFβ1、TGFβ2、TGFβ3 因子的变化情况。结果:淤给予相应细胞处理,可见过表达IDO-BMSCs 处理后2 d 移植心脏的EF、FS 较其余各组有提高。于采用小动物活体评估可见过表达IDO-BMSCs 组移植心脏局部荧光强度最强。盂给予干预措施后2 d 可见过表达IDO-BMSCs 组脾脏细胞CD40、CD86、CD80、MHCⅠ、CD45RA、CD45RA+CD45RB 表达降低,而CD274、Treg 细胞的表达增高。榆采用液相芯片检测各组提取血清可见在2 d 时,过表达IDO-BMSCs 组血清中IL-1α、IL-4、IL-1β、IL-2、IFN-γ、IL-18 是降低的;IL-10、TGFβ1、TGFβ2、TGFβ3 表达量是升高的。HE 染色证实过表达IDO-BMSCs 组炎性细胞浸润少于其他组。结论:过表达IDO 的BMSCs 可以通过有效调节免疫DC、T 细胞及细胞因子,从多个免疫层面改善移植心脏存活。     

骨髓间充质干细胞-脱细胞真皮基质对大鼠表皮缺损的修复

目的研究骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMSC)-脱细胞真皮基质(acellular dermal matrix,ADM)对SD大鼠皮肤表皮缺损的修复。方法培养SD大鼠骨髓细胞,增殖提纯传代至4代时,成骨成脂,流式细胞仪检测鉴定BMSC,然后将其接种到ADM,2d后移植到皮肤表皮缺损的SD大鼠体内,连续5周观察其修复效果。结果 BMSC-ADM修复SD大鼠皮肤表皮缺损效果良好,5周后,肉眼可见材料与组织结合紧密,有弹性,颜色接近皮肤。结论 BMSC-ADM可以作为修复SD大鼠皮肤表皮缺损的组织工程材料。     

中华小型猪心肌梗死后移植同种异体骨髓间充质干细胞归巢时间窗

背景：心肌梗死后不同时间点进行骨髓间充质干细胞移植,其归巢至损伤组织的能力以及起到的修复作用将有很大的不同。 目的：探索心肌梗死后移植的骨髓间充质干细胞归巢于心肌组织的最佳时间窗。 方法：将18头中华小型猪采用开胸结扎左冠状动脉前降支的方法建立急性心肌梗死模型。造模成功后1 d,3 d,1周,2周,3周,4周6个时间点经冠状动脉注射BrdU标记的骨髓间充质干细胞,于移植后3 d处死动物,检测心肌梗死区骨髓间充质干细胞的归巢量。 结果与结论：心肌梗死后1 d,3 d,1周,2周,3周,4周均可见有细胞核呈棕黄色的BrdU标记的阳性细胞,其中心肌梗死后1周的阳性细胞分布最多且最集中,高于其他5个时间点(P < 0.05)。说明骨髓间充质干细胞归巢的最佳时间窗为心肌梗死后1周,在此时间点给予干细胞移植促进心肌修复有一定意义。 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：     

内源骨髓间充质干细胞在心肌梗死后的迁移、归巢与分化

背景：目前的大多数研究主要集中在移植外源干细胞来源的心肌细胞对受损心肌进行修复与再生,而有关内源干细胞迁移、归巢及分化的研究比较少。 目的：观察内源骨髓间充质干细胞在心肌梗死后迁移、归巢以及分化情况。 方法：成年雌性C57BL/6小鼠随机分为2组：心肌梗死组(n=4)小鼠建立骨髓重建模型,于骨髓重建4周后行冠状动脉左前降支结扎术建立急性心肌梗死模型,1周后处死;对照组(n=3)小鼠进行单纯骨髓重建,于骨髓重建4周后处死。取心脏组织,采用免疫荧光染色检测心肌特异性蛋白Troponin Ⅰ的表达,观察心肌梗死后表达绿色荧光蛋白的骨髓间充质干细胞在心肌组织中的分布、分化情况。 结果与结论：骨髓重建小鼠心肌梗死组与对照组均可见到发绿色荧光的骨髓间充质干细胞,心肌梗死组骨髓间充质干细胞数量比对照组明显增多。两组切片均可见部分骨髓间充质干细胞呈GFP、Troponin Ⅰ和PI三阳性,心肌梗死组三阳性的细胞比对照组明显增多,表明心肌梗死后内源骨髓间充质干细胞能迁移、归巢到受损的心肌组织并获得心肌分化表型。     

骨髓间充质干细胞调节心脏移植大鼠的免疫功能

BACKGROUND:Heart transplantation is an effective method for treatment of end-stage heart failure, but immune rejection that seriously impact therapeutic effacicy is easy to occur after transplantation. OBJECTIVE:To investigate the regulatory effect of bone marrow mesenchymal stem cells on the immune function of rats undergoiong heart transplantation. METHODS:Twenty Lewis rats were enrolled as donors, and 20 Wistar rats as recipients. Heart transplantation models were established in the Wistar rats. These 20 model rats were randomized into cell transplantation and control group with 10 rats in each group. Forty-eight hours after heart transplantation, rats in the cell transplantation group were given bone marrow mesenchymal stem cell suspension (1 mL, 2×10⁸ cells/L) via the tail vein, while rats in the control group were given normal saline in the same dose. Then, the expression levels of serum interleukin-2, interleukin-10 and percentage of CD4⁺, CD8⁺, CD4⁺/CD8⁺, CD4⁺CD25^high, CD4⁺CD25^high Foxp3⁺ T cells in the venous blood were detected in the two groups at 7 days after cell transplantation. Additionally, rat myocardial tissues were taken and observed pathologically. RESULTS AND CONCLUSION:The survival time of the cell transplantation group was significantly longer than that of the control group (P < 0.05). The expression level of interleukin-2 showed no significant difference between the two groups (P > 0.05), but the level of interleukin-10 in the cell transplantation group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the percentage of CD4⁺/CD8⁺, CD4⁺CD25^high, CD4⁺CD25^high Foxp3⁺ and CD4⁺ T cells was significantly higher, and the percentage of CD8⁺ T cells was significantly lower in the cell transplantation group (P < 0.05). Histopathological findings showed that there were a small amount of infiltrated lymphocytes in the cell transplantation group with the presence of slight bleeding and edema, and these inflammatory reactions were milder than those in the control group. These findings indicate that bone marrow mesenchymal stem cell transplantation can effectively reduce the rejection in rats undergoing heart transplantation.     

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.     

同种异体骨髓间充质干细胞移植在心肌梗死后心室重建中的作用

BACKGROUND:Myocardial infarction leads to ischemic changes in the myocardium, triggering the emergence of ventricular remodeling, which is an important cause of death. Myocardial infarction is a common disease in the middle-aged and elderly population, but autologous bone marrow mesenchymal stem cells from these patients exhibit a weak ability of proliferation and differentiation. Therefore, a positive attempt of allogeneic stem cell transplantation is required in order to obtain better therapeutic outcomes. OBJECTIVE:To explore the effect of allogeneic bone marrow mesenchymal stem cells on ventricular remodeling after myocardial infarction.   METHODS:Bone marrow mesenchymal stem cells from 10 neonatal rats and 10 adult rats were isolated, cultured and identified. Another 40 rats were randomly assigned into four groups (n=10/group): model group, neonatal rat cell transplantation group, adult rat cell transplantation group, or sham group. Animal models of myocardial infarction were made in rats in the all groups except for the sham group in which the rats were given sham operation. Rats in the two cell transplantation groups were given the corresponding cell transplantation. Four weeks postoperatively, heart function of rats was detected in each group, and cardiac tissues were taken to detect changes in collagen formation and blood vessel density in the infarct area. RESULTS AND CONCLUSION:Four weeks after surgery, rats in the model group showed significant changes in cardiac function indexes as compared with the other groups (P < 0.05), while compared with the model group, these cardiac function indexes improved in both two cell transplantation groups, but there was no significant difference between the two cell transplantation groups (P > 0.05). Meanwhile, compared with the model group, significantly decreased collagen formation and increased blood vessel density were found in both two cell transplantation groups (P < 0.05). Additionally, the vascular density of the infarct area was highest in the sham group (P < 0.05). Experimental results show that both neonatal and adult rat bone marrow mesenchymal stem cell transplantation can improve cardiac function of rats, reduce the formation of collagen in the infarct area and delay ventricular remodeling after myocardial infarction.     

关节腔注射自体骨髓间充质干细胞治疗轻中度骨性关节炎

背景：大量来源于动物实验或实验室的证据表明骨髓间充质干细胞具有强有力的免疫抑制、抗炎症、软骨再生能力。但是相对于动物实验,骨关节炎患者的关节微环境更复杂,涉及大量的生物活性因子及免疫机制。目的：分析经皮穿刺关节腔注射自体骨髓间充质干细胞治疗轻中度骨性关节炎患者的疗效,探讨其炎症抑制、免疫调节、缓解软骨降解等机制。方法：收集26例轻中度骨性关节炎患者骨髓15 mL,在实验室分离、培养、获得足量的骨髓间充质干细胞,并以流式细胞仪检测其表面标志物,分析其体外诱导成骨、成脂分化能力。26例患者双侧膝关节分别入组实验组及对照组,实验组膝注射自体来源的体外培养的骨髓间充质干细胞(2×10⁷个),对照组则注射等量不含细胞安慰剂。采用WOMAC评分评价治疗前后膝关节功能变化。在治疗前、治疗后2周,利用ELISA检测关节液中白细胞介素1、肿瘤坏死因子α、白细胞介素10、软骨寡聚基质蛋白水平。结果与结论：按照标准化的细胞分离、培养扩增方案,能获得足量的用于关节腔注射的骨髓间充质干细胞(超过2×10⁷第3代细胞)。从患者分离出来的骨髓间充质干细胞均阳性表达CD105、CD29,阴性表达CD45、CD34,体外具有良好的成骨、成脂能力。治疗后患者的膝关节功能明显改善,而且相对于对照组,实验组关节液中白细胞介素1、肿瘤坏死因子α、软骨寡聚基质蛋白水平明显下降,而白细胞介素10水平上升。以上结果表明,关节腔注射自体骨髓间充质干细胞治疗轻中度骨性关节炎具有良好的疗效,进一步推测注射到关节腔内的骨髓间充质干细胞有可能通过炎症抑制及逆转软骨降解等机制发挥作用,从而有望成为治疗轻中度骨性关节炎有效、可行的方法。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：     

灯盏花素联合骨髓间充质干细胞移植促进脑梗死大鼠神经功能恢复

背景：灯盏花素治疗脑梗死疗效确切、不良反应少、远期疗效稳定、毒副作用少,能够改善脑梗死后中枢神经系统受损区的微环境。 目的：探讨灯盏花素注射液联合骨髓间充质干细胞移植对脑梗死神经功能恢复及生长相关蛋白43表达的影响。 方法：将60只大脑中动脉闭塞模型SD大鼠随机分为脑梗死组、骨髓间充质干细胞移植组和联合组。建模6 h后通过尾静脉注射1 mL PBS、1 mL骨髓间充质干细胞悬液(2.5×106)、1 mL骨髓间充质干细胞悬液(2.5× 106)+灯盏花素注射液75 mg/kg,连续注射5 d,1次/d。 结果与结论：移植后2周,免疫荧光法观察到BrdU阳性标记的骨髓间充质干细胞主要集中于梗死灶周围且联合组的BrdU阳性细胞数量多于骨髓间充质干细胞组及脑梗死组(P < 0.01);移植后1,2,3周联合组的神经功能障碍评分明显低于骨髓间充质干细胞组及脑梗死组(P < 0.05);移植后2周,与骨髓间充质干细胞组及脑梗死组比较,联合组的脑梗死面积明显减小,水肿程度明显减轻,生长相关蛋白43的表达明显增高(P < 0.05)。光镜下联合组脑梗死组织中胶质细胞明显增生,脑组织水肿有明显减轻。结果表明灯盏花素注射液联合骨髓间充质干细胞可明显减轻脑梗死面积及水肿程度,促进大鼠脑梗死后神经功能恢复及梗死灶生长相关蛋白43的表达。 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     

PTEN基因沉默骨髓间充质干细胞移植治疗急性心肌梗死

BACKGROUND:Bone marrow mesenchymal stem cell transplantation for myocardial infarction becomes popularized in recent years, but transplanted cells cannot survive and proliferate under early inflammatory reaction or local ischemia/hypoxia microenvironment, eventually hampering the therapeutic outcomes. OBJECTIVE:To investigate the therapeutic effect of PTEN-silenced bone marrow mesenchymal stem cells on acute myocardial infarction. METHODS:(1) Bone marrow mesenchymal stem cells from Sprague-Dawley rats were randomly assigned to receive no treatment, NCsiRNA transfection using Lipofectamin2000 or PTEN siRNA transfection using Lipofectamin2000. Cell growth curves were described using MTT method to detect cell cycle using flow cytometry. (2) Thirty Sprague-Dawley rats were selected to prepare myocardial infarction models that were randomized into three groups (n=10 per group): blank control, negative control and RNAi group. Six hours after modeling, bone marrow mesenchymal stem cells transfected with nothing, NCsiRNA and PTEN siRNA were respectively injected into the infarcted center of the left ventricular anterior wall in these three rat groups. After 4 weeks, all rats were subjected to cardiac function detection using echocardiography, and the survival and proliferation of bone marrow mesenchymal stem cells in the rats were observed by fluorescence microscopy. RESULTS AND CONCLUSION:Compared with the other two groups, a significant increase in the absorbance values at different culture time, the proportion of cells in S+G2 phase, and the number of bone marrow mesenchymal stem cells in the myocardial tissue was found in the RNAi group (all P < 0.05). Additionally, the left ventricular ejection fraction and left ventricular shortening fraction were significantly reduced in the RNAi group than the blank control and negative control groups at 4 weeks after cell transplantation (P < 0.05). Both in vivo and in vitro experimental findings showed that PTEN silencing could effectively improve cell survival and proliferation in the infarcted myocardium. Moreover, in the in vivo experiment, an overt improvement in rat’s cardiac function was achieved.      

骨髓间充质干细胞移植脑梗死模型后的CT、MRI特征分析

背景：研究表明骨髓间充质干细胞可通过多种途径发挥促进脑组织功能恢复的作用。 目的：分析骨髓间充质干细胞移植脑梗死模型大鼠的CT、MRI特征。 方法：将40只脑梗死模型大鼠随机分为2组,梗死组通过尾静脉注射1 mL PBS、移植组通过尾静脉注射1 mL细胞浓度为2.0×109 L-1的细胞悬液。于移植后1,2,3周进行神经功能缺损评分(mNSS),评价神经功能恢复情况;于移植后的6 h,1,3,5,7 d对各组大鼠行CT及MRI扫描,观察脑梗死区TIWI、T2WI、FLAIR、DWI序列的信号改变特征,梗死体积大小。测量脑梗死区域T1WI、T2WI、FLAIR、DWI序列的信号强度比(SIR)及其相对变化率(?SIR),并与正常对侧相应解剖区域进行比较。 结果与结论：移植后1,2,3周,移植组的神经功能缺损评分明显低于梗死组(P < 0.05);移植后3,5,7 d时移植组脑梗死体积较梗死组显著减少(P < 0.05),移植组T1WI序列SIR均明显高于梗死组,T2WI、FLAIR序列SIR较梗死组显著降低,差异有显著性意义(P < 0.05);移植后7 d时移植组DWI序列SIR较梗死组明显降低(P < 0.05)。移植组T1WI序列?SIR与梗死组比较差异无显著性意义(P > 0.05),移植组T2WI、FLAIR及DWI序列?SIR较梗死组显著增高,差异有显著性意义(P < 0.05)。结果显示MRI可显示大脑任意角度的切面像,对骨髓间充质干细胞移植治疗脑梗死的疗效评价起重要作用。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