骨髓间充质干细胞静脉移植对扩张型心肌病大鼠毛细血管生成的影响

目的观察骨髓间充质干细胞（MSCs）经静脉途径移植对阿霉素诱导的扩张型心肌病（DCM）大鼠心功能的影响。方法建立大鼠阿霉素性心肌病模型,随机分为三组：DCM空白组（B组）、静脉移植组（C组）和静脉对照组（D组）,另设正常对照组（A组）。经尾静脉注射在体外扩增并DAPI标记的骨髓间充质干细胞和培养基至C组和D组大鼠,A组和B组大鼠不干预。移植后8周心脏彩超观察左室舒张末径（LVDD）、左室射血分数（LVEF）,多导生理记录仪观察左室最大压力上升速率（＋LVdp/dtmax）、左室最大压力下降速率（-LVdp/dtmax）,并分析组织病理学特征。结果细胞移植后8周,C组LVEF高于B组和D组;LVDD稍低于B组和D组;＋LVdp/dtmax明显高于B组,也显著高于D组;-LVdp/dtmax明显高于B组和D组;C组心肌中可见带有蓝色荧光的DAPI标记的骨髓MSCs,心肌胶原容积百分比低于B组和D组,毛细血管计数高于B组和D组;C组VEGF水平明显高于B组和D组。结论骨髓MSCs静脉移植治疗阿霉素诱导的扩张型心肌病大鼠,提高VEGF水平,促进心肌毛细血管新生,减少胶原纤维,改善心功能。     

骨髓间充质干细胞自体移植治疗阿霉素心肌病

目的:探讨骨髓间充质干细胞(MSCs)自体移植入兔阿霉素(ADR)心肌病心肌后的微环境依赖性分化及对心功能的影响。方法:日本大耳白兔随机分为:心肌病自体细胞移植组(n=10),心肌病对照组(n=8)及假手术组(n=6)。将自体MSCs和同体积的培养基分别移植入前两组动物心肌内,假手术组仅作开胸术而无移植。术后4周行心功能及组织学检测。结果:与假手术组相比,心肌病组的心功能明显降低;与心肌病对照组相比,自体移植组的心功能有显著改善,并在移植部位发现移植细胞有心肌肌钙蛋白T的表达。结论:MSCs移植入ADR心肌病的心肌组织中后,可在其微环境中存活并分化为心肌样细胞,并显著改善左室功能。     

骨髓间充质干细胞移植治疗大鼠扩张型心肌病

1泸州医学院附属医院急诊科,四川省泸州市 646000;2哈尔滨医科大学附属第二医院心内科,黑龙江省哈尔滨市  150000 背景：扩张型心肌病所致的心肌纤维化是心力衰竭的病理基础,目前药物治疗、介入治疗和外科手术均不能替代坏死心肌和彻底改善心脏功能。 目的：观察异体骨髓间充质干细胞移植对大鼠扩张型心肌病心脏功能的作用和心肌纤维化的影响。 方法：40只Wistar大鼠随机数字表法分为细胞移植组(n=15)、对照组(n=15)和空白组(n=10),前2组建立大鼠扩张型心肌病模型。造模成功4周后细胞移植组注射骨髓间充质干细胞悬液150 μL(含3×106个细胞),对照组和空白组注射等量培养液。 结果与结论：与空白组相比,细胞移植组和对照组移植前左室收缩末期内径增加,射血分数和缩短分数明显下降(P < 0.01);移植后4周,细胞移植组超声心动图检查和移植前相比,左室收缩末期内径下降、射血分数和缩短分数明显升高(P < 0.01)。细胞移植组心脏胶原的表达低于对照组(P < 0.05)。与对照组相比,其他2组基质金属蛋白酶2及基质金属蛋白酶9表达明显下降(P < 0.05)。提示骨髓间充质干细胞移植后可改善心肌纤维化及扩张型心肌病鼠的心脏功能。      

骨髓间充质干细胞静脉移植治疗大鼠脊髓损伤

背景：干细胞移植可以重建中枢神经系统的结构和功能,近年来引起了广泛的关注。 目的：尾静脉移植骨髓间充质干细胞观察其对大鼠脊髓损伤修复的影响并探讨其机制。 方法：密度梯度离心法结合贴壁筛选法分离骨髓间充质干细胞。将成年雌性Wistar大鼠以动脉瘤夹钳夹法制备大鼠脊髓损伤模型后随机分为细胞移植组和对照组,分别干预。 结果与结论：细胞移植组大鼠BBB后肢功能评分恢复优于对照组(P < 0.05)。自损伤后第30天开始,细胞移植组大鼠运动诱发电位潜伏期及体感诱发电位P1波潜伏期的恢复均优于对照组(P < 0.05),并持续至实验结束。细胞移植组大鼠脊髓内在损伤中心及头、尾端距离脊髓损伤中心1 cm处均可见阳性细胞。说明尾静脉注射移植骨髓间充质干细胞可以促进脊髓损伤大鼠神经功能恢复,其机制可能与移植细胞迁移到损伤部位,分化为神经元样和神经胶质细胞样细胞,并分泌或促进宿主分泌神经营养因子有关。     

骨髓间充质干细胞移植治疗肝硬化的研究进展

肝硬化是临床中常见的慢性进行性肝病,目前治疗晚期肝硬化最有效的方法是肝脏移植,但肝源缺乏、费用昂贵、移植排斥反应及长期应用免疫抑制剂引起并发症等成为限制其广泛应用的主要原因.干细胞移植有利于受损肝组织修复,能够代偿部分肝功能,已成为治疗肝病的一种新方法.就骨髓间充质干细胞移植治疗肝硬化的基础、临床研究进展、存在的问题以及发展前景作一综述,旨在为其进一步研究提供理论依据.     

骨髓间充质干细胞移植治疗骨质疏松的研究进展

骨质疏松症被定义为一种系统性骨骼疾病,其特征是骨量低、骨组织微结构恶化、骨脆性和骨折易感性增加。 目前有2亿多人患有骨质疏松症,但由于人口老龄化和人均寿命延长,受影响的人数仍在急剧增加,这是一个重大的公共卫生问题。目前,治疗骨质疏松症的药物开发已经取得了重大进展,但药物治疗并不能逆转骨丢失,且会给患者带来一系列毒副作用。大量研究表明,骨髓间充质干细胞的归巢作用、成骨分化和细胞因子作用在骨质疏松发病过程中发挥重要作用。 移植骨髓间充质干细胞作为一种新方法,不仅能避开药物治疗的副作用而且能从根本上治疗骨质疏松,具有巨大的潜能和应用价值,但许多问题也有待解决。     

人脐血间充质干细胞尾静脉移植治疗扩张型心肌病

背景：体外研究表明人脐血间充质干细胞可分化为自律性跳动的心肌细胞,而经静脉移植人脐血间充质干细胞治疗扩张型心肌病心力衰竭的报道较少。 目的：探讨经尾静脉移植人脐血间充质干细胞对扩张型心肌病大鼠心肌结构、心功能的影响。 方法：Wistar大鼠通过腹腔注射阿霉素诱导扩张型心肌病模型,扩张型心肌病实验组于造模后8周经尾静脉移植人脐血间充质干细胞,扩张型心肌病对照组注射等量DMEM培养基。健康对照组不造模,于相同时间点注射等体积的生理盐水。 结果与结论：与健康对照组相比,扩张型心肌病组心功能明显受损,且扩张型心肌病实验组受损较扩张型心肌病对照组轻;移植的细胞有肌钙蛋白T的表达。结果提示人脐血间充质干细胞移植能促进扩张型心肌病大鼠心功能恢复,使心肌组织病变减轻。     

骨髓间充质干细胞移植后的肝功能重建

背景：细胞移植是治疗肝功能衰竭的一种有效方法,而理想的细胞源和最佳的移植途径一直是各实验室不断研究的目标。 目的：观察骨髓间充质干细胞移植对急性肝衰竭大鼠肝功能重建的影响和最佳移植途径。 方法：以D-氨基半乳糖胺作为肝脏毒剂,构建雌性SD大鼠急性肝衰竭模型。以雄性SD大鼠骨髓间充质干细胞为细胞源,通过腹股沟静脉和脾内移植两种途径植入肝衰竭大鼠,动态检测多项肝功能血生化指标。并以sry基因为分子标志,采用PCR技术检测骨髓间充质干细胞在肝脏内的存活状态。 结果与结论：骨髓间充质干细胞经腹股沟静脉和脾内移植均可降低血清谷丙转氨酶、谷草转氨酶、总胆红素水平,提高白蛋白合成能力,改善肝功能,降低动物死亡率。经腹股沟静脉移植组死亡率低于经脾内移植组。移植后7~30 d在受体大鼠肝脏内均能检测到sry基因阳性细胞的存在,而相应对照组未能检测到sry基因阳性细胞。结果表明①骨髓间充质干细胞移植可改善急性肝衰竭大鼠的肝功能。②骨髓间充质干细胞可在受体肝脏内存活。③经腹股沟静脉移植操作简便易行,死亡率较低,是较好的细胞移植途径。     

骨髓间充质干细胞移植治疗缺血性脑卒中的研究进展

骨髓间充质干细胞（BMSCs）是一种具有多向分化和增殖潜能的干细胞,在体内、外均能分化出神经细胞。近年来,BMSCs移植治疗缺血性脑卒中的动物实验和临床研究都取得了较好效果,已成为治疗神经系统疾病的一种新技术,具有广阔的发展前景。本文将就骨髓间充质干细胞的生物学特征及其移植治疗缺血性脑卒中的作用及机理予以综述。     

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.     

骨髓间充质干细胞在微损伤环境中修复骨不连

背景：骨髓干细胞能够增殖再生,与传统的手术治疗方案结合能明显增强骨不连的治疗效果,具有重要的应用价值。 目的：探讨骨髓间充质干细胞在微损伤环境中对骨不连的治疗效果。 方法：选取清洁级纯种新西兰大白兔40只,采用随机数字表法分为实验组与对照组,每组20只。按照手术操作流程获取胫骨骨髓,分离培养骨髓间充质干细胞,待细胞增殖到第3代够107数量级时,进行超顺磁氧化铁纳米粒子培养标记。在兔前肢桡骨中段约15 mm处造成骨缺损,骨缺损6周发生骨不连。实验组大白兔将骨髓间充质干细胞与髂骨碎粒一起植入骨缺损处。对照组不进行干细胞移植,于骨缺损处植入髂骨碎粒。术后12周内,观察大白兔骨不连部位大体形态、X射线片、病理学染色结果。 结果与结论：实验组术后明显发现骨痂,骨缺损处逐渐修复,直至完全愈合;对照组大白兔骨不连部位没有骨痂,骨髓腔封闭,充填肉芽组织。实验组有增生活跃的软骨组织,碎粒融合,骨缺损处出现类骨质,成骨细胞进行性增加;对照组软骨增生差,有大量死骨,骨粒未融合,没有成骨细胞。实验组桡骨缺损部位X射线显示云雾状影,骨髓腔恢复再通,骨骼塑形好;对照组骨碎粒吸收较少,骨髓腔部分闭塞,骨骼未连接,缺损处硬化。结果显示在局部微损伤环境中,骨髓间充质干细胞能够增殖分化为成骨细胞,修复骨缺损导致的骨不连具有显著效果。 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     

移植骨髓间充质干细胞肝癌大鼠细胞凋亡及炎症因子的动态变化

BACKGROUND:Bone marrow mesenchymal stem cell transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cells and inflammatory factor level. OBJECTIVE:To investigate the effect of rat bone marrow mesenchymal stem cells on dynamic change of inflammatory factors and cell apoptosis during hepatocarcinogenesis. METHODS:Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cell transplantation via the tail vein. Two weeks after cell transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1α detected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cell apoptosis index detected by TUNEL technique. RESULTS AND CONCLUSION:After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P < 0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cell transplantation (P < 0.05) and close to the normal levels (P > 0.05). Bone marrow mesenchymal stem cell transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1α in the liver tissue that was decreased obviously after modeling (P < 0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cells.     

骨髓间充质干细胞移植对胃癌模型大鼠肿瘤细胞的影响

BACKGROUND:Bone marrow mesenchymal stem cells can migrate into tumor tissues, as reported in recent studies. OBJECTIVE:To investigate the tropism and effect of transplantation of bone marrow mesenchymal stem cells on proliferation and differentiation of gastric cancer cell line SGC7901 in rats. METHODS:Gastric cancer models were established in Sprague-Dawley rats by subcutaneous injection of gastric cancer cell line SGC7901, and then, in cell transplantation group, each rat underwent an intraperitoneal injection of 1×107 bone marrow mesenchymal stem cells. After transplantation, the targeting ability of bone marrow mesenchymal stem cells was detected using fluorescent DiI labeling. Cyclin D2 mRNA and protein expressions were measured using real-time PCR and western blot assay, respectively. Apoptosis of gastric cancer cells was observed by in situ terminal labeling method. RESULTS AND METHODS: Bone marrow mesenchymal stem cells successfully migrated into the gastric cancer site in rats. The expression levels of cyclin D2 mRNA and protein in the cell transplantation group were significantly higher than those in the model group (P < 0.05). It was observed that the number of apoptotic cancer cells was significantly reduced in the cell transplantation group compared with the model group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cells have the ability to migrate into the tumor sites, thereby promoting the proliferation of gastric cancer cells.     

人参皂苷诱导骨髓间充质干细胞促进创伤性颅脑损伤的神经再生

背景：以往研究表明骨髓间充质干细胞治疗神经疾病方面已经取得了一定成效,能明显促进神经功能改建,但关于基因及药物调控的相关研究目前尚未取得突破性进展。 目的：探讨人参皂苷诱导骨髓间充质干细胞分化对创伤性颅脑损伤后神经再生的影响。 方法：采用液压冲击法建立大鼠颅脑创伤模型,随机分为颅脑损伤组、骨髓间充质干细胞组、人参皂苷诱导分化的骨髓间充质干细胞组。移植后2周采用Western blot检测创伤脑组织神经生长因子及脑源性神经营养因子表达水平,免疫组织化学法检测BrdU标记的阳性细胞数量;移植后1,3 d及1,2周进行动物神经学缺损评分。 结果与结论：人参皂苷诱导分化的骨髓间充质干细胞组大鼠脑创伤组织神经生长因子及脑源性神经营养因子蛋白表达水平明显高于骨髓间充质干细胞组和颅脑损伤组(P < 0.05);人参皂苷诱导分化的骨髓间充质干细胞组BrdU标记的阳性细胞数量明显多于骨髓间充质干细胞组和颅脑损伤组(P < 0.05);移植后3 d及1,2周,人参皂苷诱导分化的骨髓间充质干细胞组大鼠神经功能障碍评分低于骨髓间充质干细胞组和颅脑损伤组(P < 0.05)。结果表明经人参皂苷诱导分化后的骨髓间充质干细胞移植可以促进创伤性颅脑损伤大鼠的神经再生,较单独应用骨髓间充质干细胞移植效果显著。 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     

骨髓间充质干细胞移植对老年性痴呆行为学的影响

BACKGROUND:Drug treatment for senile dementia has unsatisfactory outcomes although to a certain extent it can reduce and delay the progression of Alzheimer’s disease. Stem cell transplantation is a new attempt for the treatment of senile dementia. OBJECTIVE:To observe the effect of bone marrow mesenchymal stem cell transplantation on the behavior of senile dementia rats. METHODS:Rat models of senile dementia were made in 20 Sprague-Dawley rats that were given continuous 60-day gavage of aluminium chloride solution. Then, model rats were randomized into model group treated with normal saline injection and experimental group treated with hippocampal injection of bone marrow mesenchymal stem cells, respectively. Another 10 rats undergoing normal feeding served as control group. Learning and memory ability of rats were tested by Morris water maze, and superoxide dismutase activity and malondialdehyde content in brain tissues of rats were measured by colorimetric method at 4 weeks after cell transplantation. RESULTS AND CONCLUSION:Compared with the model group, the escape latency was shortened and the cross-platform frequency was increased in the experimental group (P < 0.05), and moreover, significantly elevated superoxide dismutase activity and reduced malondialdehyde content in the brain tissues of rats were found in the experimental group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to behavior improvement in senile dementia rats by improving the learning and memory ability.     

骨髓间充质干细胞移植治疗老年性痴呆模型大鼠的行为学检测

BACKGROUND:More recently, studies have demonstrated that bone marrow mesenchymal stem cells can be induced in vitro to differentiate into neuron-like cells that are used for in vivo transplantation to repair nerve damage. OBJECTIVE:To study the effect of bone marrow mesenchymal stem cell transplantation on learning and memory ability of senile dementia rats. METHODS:Thirty male Sprague-Dawley rats were randomly divided into three groups: normal control group, stem cell therapy group and model control group. Rats in the latter two groups were used to establish animal models of senile dementia by intracranial injection of β-amyloid 1-40. Three weeks after modeling, rats were given bilateral hippocampal injection of induced bone marrow mesenchymal stem cell suspension in the stem cell therapy group, whereas no treatment was given in the normal control and model control groups. Morris water maze test was used to detect learning and memory ability of rats, and rat’s brain tissues were detected pathologically using hematoxylin-eosin staining. RESULTS AND CONCLUSION:After modeling, the escape latency was higher and the cross-platform frequency was lower in the model control group compared with the normal control group. After cell transplantation, the escape latency and cross-platform frequency were gradually shortened and increased with time, respectively. Compared with the model control group, the learning and memory abilities of rats were improved in the stem cell therapy group. The brain tissues were relatively intact in structure and exhibited less cell degeneration and necrosis in the stem cell therapy group compared with the model control group. To conclude, bone marrow mesenchymal stem cell transplantation exerts certain therapeutic effects on senile dementia by effectively improving the learning and memory ability.     

大黄素对骨髓间充质干细胞移植治疗缺血性再灌注肾损伤的影响

BACKGROUND: Studies have shown that emodin protects against intestinal ischemia-reperfusion injury by inhibiting the release of inflammatory factors.     

骨髓间充质干细胞移植治疗肢体缺血的机制

背景：骨髓间充质干细胞移植治疗下肢缺血疾病已取得较好的效果,但其作用机制尚无定论。 目的：探讨骨髓间充质干细胞移植治疗SD大鼠后肢缺血的机制。 方法：结扎肾动脉下腹主动脉、腰动脉和髂腰动脉制备雌性SD大鼠后肢缺血模型。将扩增、纯化的雄性SD大鼠骨髓间充质干细胞注射入大鼠缺血的右后肢股直肌中,对照组右后肢注射等量生理盐水。移植后2,4,6周,制备大鼠右股直肌切片行苏木精-伊红染色、血管内皮生长因子免疫组织化学染色、SRY基因免疫组织化学染色。 结果与结论：移植后2,4,6周移植组右股直肌毛细血管计数、血管内皮生长因子免疫组织化学染色阳性细胞计数均明显高于对照组(P < 0.01)。移植组股直肌切片中SRY免疫组织化学染色阳性细胞出现于毛细血管壁,并散在分布于肌组织中。结果表明局部注射移植骨髓间充质干细胞能促进缺血组织迅速生成大量毛细血管,改善大鼠缺血下肢的血供。骨髓间充质干细胞作为旁分泌细胞,通过增加血管内皮生长因子的分泌,促使大鼠缺血肢体的血管新生。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：