不同移植途径对人脐带间充质干细胞防治NOD鼠糖尿病的影响

目的观察不同移植途径对人脐带间充质干细胞(hUCMSCs)预防非肥胖型糖尿病(NOD)小鼠糖尿病发病的影响并进一步探索其机制。方法通过胰腺包膜下和尾静脉向4周龄雌性NOD小鼠注射hUCMSCs-EGFP/luc,活体成像观察hUCMSCs的分布。动态监测NOD小鼠血糖水平变化以及Treg/Th17细胞变化,在30周龄时处死小鼠进行胰腺炎评级。结果胰腺移植组在30周龄时糖尿病发病率显著低于尾静脉移植组和对照组。2种途径移植组小鼠Treg细胞呈升高趋势,明显高于对照组,而Th17细胞明显低于对照组,2种移植途径组间无明显差异。病理学发现胰腺组胰腺炎评分最低,对照组最高,移植组胰腺炎性损伤明显减轻。结论 hUCMSCs经2种途径移植后,均能明显降低NOD鼠糖尿病的发生率和延缓发病时间,且胰腺移植组效果显著。除hUCMSCs主要通过诱导Treg细胞抑制Th17细胞发挥免疫抑制作用,阻止自身免疫对胰岛β细胞的攻击外,可能与到达胰腺组织的细胞对胰腺β细胞的保护和损伤修复作用也具有一定关系。     

骨髓间充质干细胞移植入糖尿病大鼠胰腺后的分化及对血糖的影响

目的 骨髓间充质干细胞(BMSCs)移植入糖尿病模型鼠胰腺包膜下，观察BMSCs的分布及对糖尿病的治疗效果。方法 利用绿色荧光蛋白（EGFP）标记雄性SD大鼠BMSCs，以多点注射的方法移植入糖尿病大鼠胰腺包膜下，血糖仪监测血糖，ELISA法检测胰岛素和C-肽水平，移植后8周，通过EGFP示踪植入的BMSCs的分布，取EGFP标记的胰腺组织，免疫荧光染色检测是否存在EGFP和胰岛素共表达,荧光原位杂交检测是否存在EGFP和PDX1共表达。结果 胰腺包膜下移植BMSCs有效降低糖尿病鼠血糖，升高血清胰岛素和C肽水平（P <0.05）。至移植后8周,植入细胞稳定表达绿色荧光蛋白，EGFP标记细胞分布于胰岛（12.46%），血管（4.4%），腺泡（9.24%），导管（3.21%），或集中分布于局部（70.69%）。免疫组化发现EGFP和胰岛素共表达细胞（5.16%），荧光原位杂交发现EGFP和PDX1共表达细胞（0.96%）。结论 BMSCs胰腺包膜下移植后在胰腺中发生再分布，在胰腺微环境中能够分化为胰岛素分泌细胞，有效逆转血糖、胰岛素和C肽水平。     

大鼠胰岛素瘤实验模型的建立及其应用

目的 通过移植大鼠胰岛素瘤INS-1细胞至糖尿病小鼠肾包膜下使之形成胰岛素瘤,并诱导其发生凋亡,建立可用于研究胰岛β细胞凋亡机制的动物模型.方法 将5×106 INS-1细胞接种于链脲霉素(STZ)造模的糖尿病小鼠左肾包膜下,监测动物空腹血糖和血清胰岛素水平的变化,当血糖趋近正常后摘取动物左侧肾脏并检测其血糖和血清胰岛素水平的变化;固定包埋摘取的肾脏,进行HE染色以及胰岛素的免疫组化染色,确定胰岛素瘤模型的建立.在胰岛素瘤动物模型中,腹腔给予毒胡萝卜素(TG)或软脂酸钠(PA),监测给药后动物空腹血糖的变化,当血糖浓度出现逆转时,摘取动物左侧肾脏,通过TUNEL原位染色法检测移植瘤细胞的凋亡.结果 将INS-1细胞移植到糖尿病小鼠肾包膜下后,从第9天开始,动物空腹血糖进行性降低,血清胰岛素水平逐渐升高,当动物血糖接近至正常时,摘取动物左肾导致动物血糖显著升高,在摘取的左肾可见明显的移植瘤,免疫组织化学染色显示移植瘤细胞为胰岛素阳性.在胰岛素瘤动物模型给予TG或PA刺激后,动物空腹血糖出现逆转,显著升高,血清中胰岛素含量明显降低,摘取动物左侧肾脏后,TUNEL原位染色发现移植瘤内有明显的细胞凋亡.结论 大鼠胰岛素瘤INS-1细胞肾包膜下移植可以建立胰岛素瘤动物模型,应用此动物模型可以在体内研究胰岛β细胞凋亡的机制.     

CD133脐血干细胞对妊娠期糖尿病的影响

背景：脐血中含有大量的造血干细胞、丰富的间充质干细胞,与外周血及骨髓干细胞相比,新生儿脐血干细胞的异体排斥反应小,免疫原性低。 目的：观察CD133脐血干细胞植入治疗小鼠妊娠期糖尿病的可行性,为临床妊娠期糖尿病的治疗提供新的途径。 方法：采用高糖高脂喂养方法对孕鼠进行妊娠期糖尿病造模,流式细胞分选技术对脐血干细胞进行分离筛选。将筛选出的CD133脐血干细胞通过尾静脉植入妊娠期糖尿病小鼠体内,移植7 d后,测定小鼠空腹血糖、空腹胰岛素、总胆固醇和三酰甘油水平,采用苏木精-伊红染色观察小鼠胰腺组织的损伤和修复情况,采用胰岛素抵抗稳态模型分析小鼠胰岛素抵抗指数和胰岛功能。 结果与结论：采用流式细胞分选技术可以从脐血单核细胞中分选出CD133脐血干细胞,分选纯度可达到(90.24±2.56)%;尾静脉移植脐血干细胞7 d后,妊娠期糖尿病孕鼠总胆固醇、三酰甘油水平、空腹血糖和空腹胰岛素水平均明显下降(P < 0.05),胰岛素抵抗指数下降,胰岛功能改善(P < 0.05),孕鼠胰腺组织萎缩情况逆转,炎性浸润减少。结果表明脐血干细胞移植可以使妊娠期糖尿病病情得到改善,可能与其修复胰腺损伤、降低胰岛素抵抗指数、改善胰岛功能有关。 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     

人AAT基因在糖尿病细胞治疗中对β细胞的免疫保护作用

目的:建立稳定表达人α1-抗胰蛋白酶(hAAT)基因的NIT-hAAT细胞系,观察hAAT基因在糖尿病细胞治疗中对β细胞的免疫保护作用。方法:构建hAAT的真核表达载体,转染并筛选得到NIT-hAAT细胞系。将该细胞系移植到糖尿病模型小鼠左肾包膜下,通过检测不同移植组小鼠的血糖、血清胰岛素水平和生存期,观察不同移植细胞对糖尿病的治疗效果;RFPCR检测移植部位的hAAT表达情况以及对小鼠左肾进行石蜡切片和苏木素-伊红(HE)染色,鉴定hAAT对NIT-1细胞的免疫保护作用。结果:糖尿病小鼠接受NIT-hAAT细胞移植后,hAAT可有效延长NIT-1细胞的存活时间,使血糖明显降低并维持至正常血糖水平,小鼠的生存率也明显提高(P<0.05);移植部位的病理HE染色结果证实hAAT可明显减轻小鼠对移植物炎症反应。但RT-PCR结果显示hAAT在体内的表达量随时间增长而出现逐渐下降,NIT-hAAT细胞最终因免疫排斥反应而失去功能。结论:NIT-hAAT细胞具有明显抑制体内免疫排斥反应,可有效延长β细胞存活时间,对胰岛细胞移植具有免疫保护作用。     

人α1-抗胰蛋白酶在胰岛β细胞移植中免疫抑制和保护作用的研究

 目的：探讨人α1-抗胰蛋白酶（hAAT）蛋白在胰岛β细胞移植中的免疫抑制和保护作用。方法：构建稳定表达hAAT蛋白的NIT-hAAT细胞系。将NIT-1细胞系和NIT-hAAT细胞系分别2次腹腔注射正常BALB/c小鼠,诱导细胞毒性T淋巴细胞(CTL)产生,将丝裂霉素处理后的2种细胞系与CTL混合培养,流式细胞术检测NIT-hAAT细胞凋亡情况;ELISA检测细胞因子表达;实时荧光定量PCR检测炎症因子mRNA表达。将2种细胞系分别植入糖尿病模型小鼠左肾包膜内,动态观察血糖和体重变化、血清中胰岛素和C肽水平以及移植部位的病理学变化。结果：CTL实验中,NIT-hAAT细胞受体鼠淋巴细胞的细胞毒作用较NIT-1细胞受体鼠明显减轻。hAAT具有减轻细胞凋亡、抑制炎症因子IL-1β、IL-6 mRNA的表达以及调节Th1/Th2细胞因子平衡的作用。NIT-hAAT细胞移植到糖尿病模型小鼠后,血糖明显下降并维持至28 d,血清中胰岛素和C肽含量明显升高,移植部位炎症细胞浸润明显减轻。结论：hAAT蛋白可减轻CTL对β细胞的杀伤作用,抑制炎症因子的表达,短期内可以抑制移植物免疫排斥反应,对胰岛β细胞移植治疗糖尿病具有明显的免疫抑制和保护作用。     

糖尿病牙周炎昆明系模型小鼠牙周组织中脂联素的表达

背景：脂联素与牙周炎和2型糖尿病发病有密切关系。 目的：检测糖尿病牙周炎昆明系小鼠牙周组织中脂联素表达的变化及对牙周组织病理形态及预后的影响。 方法：将3周龄的昆明系小鼠按不同造模方式分随机为3组：对照组正常饲养,糖尿病组通过四氧嘧啶注射法建立2型糖尿病模型小鼠,糖尿病+牙周炎组采用牙周局部结扎联合涂菌建立牙周炎模型小鼠。 结果与结论：造模后20 d,糖尿病组小鼠血糖、空腹胰岛素水平及胰岛素抵抗指数高于对照组(P < 0.05)。ELISA法、RT-PCR、western lot检测显示,造模1,3,6个月后,脂联素基因及蛋白的表达对照组>糖尿病组>糖尿病伴牙周炎组小鼠牙周组织中表达水平依次减弱(P < 0.05)。造模1,3,6个月后,取3组小鼠的牙周组织通过直接观察牙龈组织炎症变化及病理组织学检测显示,糖尿病伴牙周炎组小鼠牙周组织炎细胞浸润最明显、在糖尿病组部分小鼠可见中度牙龈组织炎症、对照组小鼠牙周组织未见炎细胞浸润。结果表明,糖尿病后牙周组织脂联素表达降低是牙周炎发病及加重的重要因素之一。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

PDX1联合NKX6.1促进骨髓间充质干细胞分化为胰岛β样细胞

目的： 为提高骨髓间充质干细胞(BMSCs)向胰腺β样细胞的分化效率,以产生足够用于移植的胰岛样细胞。方法: 构建含PDX1与NKX6.1双基因的重组腺病毒载体,用重组腺病毒感染并联合多种细胞因子分步诱导BMSCs。用RT-PCR、Western blotting等多种方法分别检测PDX1、NKX6.1、胰岛素及C-肽表达情况;观测植入鼠肾包膜下的细胞形态与胰岛素、C-肽等相应分子表达情况以及检测植入细胞对糖尿病模型大鼠的血糖水平的调节能力。结果: BMSCs经重组腺病毒pAdxsi-CMV-PDX1/CMV-NKX6.1联合相应细胞因子分步诱导,双硫腙染色细胞质呈亮红色,RT-PCR显示诱导后的细胞持续稳定表达胰岛素、葡萄糖转运蛋白2(GLUT2)等β细胞相关分子;Western blotting、免疫细胞化学与间接荧光结果亦相似。所诱导的实验组细胞经5.5和25mmol/L葡萄糖刺激后胰岛素分泌水平分别为(1 240.4±109.3) mU/L和(3 539.8±245.1) mU/L, 并显著高于对照组的分泌量。移植实验组细胞可恢复STZ糖尿病小鼠血糖正常水平。结论: PDX1与NKX6.1联合细胞因子在体外能有效地诱导BMSCs分化为胰岛β样细胞;这种胰岛β样细胞移植能有效恢复STZ糖尿病小鼠的血糖正常水平,维持小鼠良好的生存状态,这将为治疗糖尿病带来新的希望。     

FADDDEL-GFP基因修饰在小鼠胰岛细胞移植中的作用

目的 探讨融合蛋白FADDDEL-GFP在胰岛细胞移植治疗1型糖尿病中的作用。方法 将重组子FADDDEL-GFP导入胰岛细胞NIT-1，检测基因转染前后胰岛细胞分泌胰岛素的水平。用STZ诱导1型糖尿病模型小鼠，将FADDDEL-GFP修饰的NIT-fg细胞移植于糖尿病小鼠，检测胰岛细胞移植后对糖尿病小鼠的影响。结果 转染重组子FADDDEL-GFP的NIT-1可见绿色荧光蛋白表达；移植NIT-fg细胞的糖尿病小鼠血糖降至正常，生存期延长，与对照组有明显差异。结论FADDDEL-GFP可增强机体抗同种移植排斥反应的能力。     

骨髓间充质干细胞胰腺内移植治疗糖尿病:是否发生了细胞的“转分化”?

背景:近年来大量研究认为骨髓间充质干细胞植入后可以改善糖尿病鼠的高血糖状态,但相关的机制尚不明确且存在一些争议。目的:探讨骨髓间充质干细胞移植到糖尿病大鼠胰腺后的作用机制。方法:将增强型绿色荧光蛋白标记的骨髓间充质干细胞移植到糖尿病大鼠胰腺包膜下,血糖仪监测血糖,RT-PCR动态检测受体鼠胰腺组织增强型绿色荧光蛋白阳性细胞中关键转录因子的表达,免疫荧光染色观察胰腺组织中增强型绿色荧光蛋白和胰岛素共表达情况,流式细胞术分析增强型绿色荧光蛋白阳性胰腺组织细胞的细胞周期和DNA倍性。结果与结论:胰腺包膜下移植骨髓间充质干细胞能有效降低糖尿病鼠血糖;Nestin、Nkx 2.2的表达分别在移植后1,3周到达峰值,Pax 4和Ngn 3的表达在移植后4周到达峰值,胰岛素和胰高血糖素的表达至移植后12周到达峰值,PDX-1的表达在8周时达到峰值并维持至12周;免疫荧光染色发现有增强型绿色荧光蛋白和胰岛素共表达细胞;流式细胞术测定增强型绿色荧光蛋白阳性的胰腺组织细胞中处于S+G2/M期的细胞增加,细胞核型未见多倍体或非整倍体细胞。提示在胰腺微环境中,植入糖尿病鼠胰腺局部的骨髓间充质干细胞在基因调控下向胰岛β样细胞发生横向转分化,而非细胞融合获得β细胞的功能表型。     

人脐带间充质干细胞移植对慢性应激模型小鼠抑郁行为的改善作用

目的 探讨人脐带间充质干细胞(hUCMSCs)尾静脉移植对慢性不可预测性温和应激(CUMS)模型小鼠抑郁行为的改善作用.方法 获得第3代hUCMSCs;将60只C57BL/6雄性小鼠随机分为正常组、模型组(给予生理盐水)、细胞组(移植hUCMSCs)、氟西汀(flu)给药组(给予flu),每组15只.构建6周CUMS小...     

小鼠胚胎胰腺移植治疗糖尿病

背景：胚胎胰腺组织具有来源广泛,细胞增殖分化能力强,低免疫排斥性等优点。 目的：探索小鼠胚胎胰腺组织的分离技术,观察其对糖尿病模型小鼠的血糖调节作用。 方法：体视显微镜下分离E11.5~E16.5 C57BL/6小鼠胰腺组织。链唑霉素诱导雄性C57BL/6小鼠建立糖尿病模型,随机分为2组：移植组模型小鼠肾被膜下移植5个E16.5胰腺组织,假手术组模型小鼠肾被膜下注入0.05 mL RPMI1640培养液。移植组小鼠血糖水平≤11.2 mmol/L后,利用IPGTT和IPITT方法检测移植后胚胎胰腺组织的内分泌功能,并摘除移植物观察血糖变化。 结果与结论：体视显微镜下可分离出较完整的E11.5~E16.5小鼠胰腺组织,≤ E12.5 d小鼠胚胎胰腺组织的形态和颜色均难以与周围组织分辨,需根据其与毗邻脏器的关系仔细辨别;> E12.5 d的小鼠胚胎胰腺已初具形态,颜色略发白。组织学和ELISA分别显示胚胎胰腺组织可表达并分泌胰岛素,其表达强度随发育时间逐渐增加。E16.5小鼠胰腺组织移植能有效地控制受体的血糖水平,使受体的体质量和糖耐量恢复正常;胚胎胰腺在受体的肾被膜下可生长发育,摘除的移植物胰岛素和胰高血糖素的表达均较移植前增强。说明胚胎胰腺组织可能成为治疗糖尿病的种子来源。     

骨髓间充质干细胞移植对糖尿病模型大鼠肾脏的保护作用

BACKGROUND:So far numerous theoretical studies have shown the treatment effect of stem cell transplantation for chronic complications of diabetes, while its treatment effects on diabetic nephropathy have not yet been confirmed in animal models. OBJECTIVE:To investigate the protective effect of bone marrow mesenchymal stem cell transplantation on the kidney in rat models of diabetes. METHODS:Rats were fed with high-sugar and high-fat diet for 4 weeks, and then were given injection of streptozotocin to establish type 2 diabetic rat models. At 2 days after modeling, bone marrow mesenchymal stem cells were injected via the tail vein (stem cell transplantation group). In the meanwhile, control and diabetes groups were established. At 21 days after cell transplantation, levels of glucose, triglyceride and insulin in the tail vein were detected. Additionally, morphological observations of kidney and pancreatic tissues were performed. RESULTS AND CONCLUSION:The levels of blood sugar, insulin and triglycerides in the diabetes group were significantly higher than those of the control group (P < 0.05). Blood glucose and insulin levels in the stem cell transplantation group were significantly lower than those of the diabetes group (P < 0.05). In addition, mesangial area and glomerular volume in the stem cell transplantation group were significantly lower compared with the diabetes group (P < 0.05). These results confirm that bone marrow mesenchymal stem cell transplantation can reduce levels of blood glucose and serum insulin, contributing to the repair of damaged pancreas and kidney.     

骨髓间充质干细胞移植治疗重症急性胰腺炎肺损伤

BACKGROUND:A large number of studies have confirmed that bone marrow mesenchymal stem cells can couple with the circulation of the blood to other organs, promote pancreatic tissue repair injury and reduce pulmonary fibrosis, which have certain therapeutic effects on pancreas and lung injuries. OBJECTIVE:To study the therapeutic effect on severe acute pancreatitis-associated lung injury in rats after the transplantation of bone marrow mesenchymal stem cells. METHODS:Animal models of severe acute pancreatitis-associated lung injury were prepared in rats via retrograde injection of 4% sodium taurocholate. Sprague-Dawley rats were randomized into three groups and received bone marrow mesencnymal stem cell injection via the tail vein in transplantation group, the same volume of normal saline in control group, or no treatment in normal groups. All the treatments in each group were performed 24 hours after modeling. Twenty-four hours after transplantation, hematoxylin-eosin staining of the pancreatic and lung tissues was performed. mRNA expressions of tumor necrosis factor-α and interleukin-1β in pancreatic and lung tissues were detected. ELISA kit was used to detect levels of serum C-reactive protein and tumor necrosis factor-α. RESULTS AND CONCLUSION:After modeling, under hematoxylin-eosin staining, there were a large number of inflammatory cells infiltrating in the damaged pancreatic tissues, accompanied by incomplete acinar structures, seriously destroyed lobular structures, alveolar fusion in the lung tissues, thickening of the alveolar walls, and a large amount of inflammatory cells infiltrating in the alveoli. These findings indicated successful modeling of severe acute pancreatitis-associated lung injury in rats. After cell transplantation, the number of infiltrated inflammatory cells in the damaged pancreatic tissue was reduced, with clear lobular structures and no bleeding from the acini; the structure of lung tissues was clear, with complete alveolar walls, and the width of alveolar space was reduced. Immunohistochemical results showed that transplanted DAPI-labeled bone marrow mesenchymal stem cells were aggregated in the pancreas and lung tissue, and uneven distributed in the damaged area. No DAPI expression in the pancreas and lung tissue was found in the control group, indicating transplanted bone marrow mesenchymal stem cells migrated into the damaged pancreas and lung tissue through the blood circulation, to further repair the damage area. RT-PCR test results showed that compared with the control group, bone marrow mesenchymal stem cell transplantation significantly reduced the levels of tumor necrosis factor-α and interleukin-1β in the pancreatic and lung tissues (P < 0.05). Higher levels of C-reactive protein and tumor necrosis factor-α were found in the control group compared with the normal group (P < 0.01), while the lower levels were obtained in the control group (P < 0.05). To conclude, our findings suggest that bone marrow mesenchymal stem cell transplantation is an effective therapy for severe acute pancreatitis-associated lung injury, and its mechanism may be associated with the reduction of inflammatory reactions and translation into the pancreas and lung tissue.     

人脐带源间充质干细胞移植改善四氯化碳诱导肝硬化大鼠的肝纤维化*☆

背景：干细胞移植作为一种全新的肝硬化治疗方法的可行性和有效性,在国内外文献中报道极少。 目的：观察人脐带源间充质干细胞移植对四氯化碳诱导肝硬化大鼠肝纤维化的影响。 方法：32只Wistar大鼠随机分为2组,对照组经尾静脉内注射生理盐水,肝硬化组采用四氯化碳植物油皮下注射8周制成肝硬化大鼠模型,再随机分为3组,盐水对照组、人脐带源间充质干细胞移植组分别经尾静脉内注射生理盐水和人脐带源间充质干细胞混悬液,8周肝硬化组无其他干预。 结果与结论：对照组血清碱性磷酸酶水平明显低于其他3组(P < 0.05);人脐带源间充质干细胞移植组血清白蛋白和胆固醇水平与对照鼠相近(P > 0.05),与8周肝硬化组和盐水对照组相比明显升高(P < 0.05)。血清碱性磷酸酶水平也出现了明显下降(P < 0.05)。肝硬化8周组大鼠肝组织中有大量胶原纤维增生并形成假小叶;盐水对照组与肝硬化8周组相似;仅在人脐带源间充质干细胞移植组大鼠肝中观察到散在的绿色抗人抗核抗体阳性细胞,肝组织中胶原纤维的量明显小于盐水对照组。提示经尾静脉移植人脐带源间充质干细胞,可明显改善四氯化碳诱导肝硬化大鼠的肝纤维化程度。 关键词：脐带源间充质干细胞;细胞移植;肝硬化;四氯化碳;大鼠 doi:10.3969/j.issn.1673-8225.2012.10.028     

移植不同剂量脐带间充质干细胞提高老年痴呆大鼠学习记忆能力的比较

BACKGROUND:To delay the onset of Alzheimer’s disease, transplantation of viable and well-differentiated stem cells is expected to repair neural tissue, which has been an issue of concern. OBJECTIVE:To explore the effects of different doses of human umbilical cord mesenchymal stem cells (hUCMSCs) on learning and memory ability of Alzheimer’s disease rats. METHODS:Fifty Sprague-Dawley rats, 7 months of age, were randomized into normal, model, high-, middle- and low-dose hUCMSCs groups (n=10 per group). Rats in model and UCMSCs groups were used to make Alzheimer’s disease animals through intraperitoneal injection of 150 mg/kg D-galactose for 90 days, and rats in the normal group were given intraperitoneal injection of normal saline for 90 days. In the three hUCMSCs group, passage 3 hUCMSCs at doses of 1×10⁵/0.2 mL/20 g, 5×10⁵/0.2 mL/20 g, and 1×10⁶/0.2 mL/20 g were injected via the tail vein, respectively. Forty-five days after cell transplantation, Morris water maze test was used to detect rat’s learning and memory abilities, and hematoxylin-eosin staining was used to observe pathological changes of the rat hippocampal CA1 region. RESULTS AND CONCLUSION:Compared with the normal group, the rats in the model group showed significant reduction in the ability of learning and memory. Compared with the model group, the escape latency was significantly shortened in the middle-dose hUCMSCs group (P < 0.05), while the number of passing times through the platform was increased significantly (P < 0.05). In the model group, the cells in the hippocampal CA1 region were arranged irregularly with unclear nucleoli and a part of cells were concentrated and deeply stained. In the middle-dose hUCMSCs group, the cells in the hippocampal CA1 region were arranged regularly with clear nucleoli, and only individual cells were stained deeply. These findings indicate that middle-dose hUCMSCs transplantation can improve the learning and memory abilities of Alzheimer’s rats.