脂肪间充质干细胞经肝动脉移植治疗晚期肝病

BACKGROUND: Stem cell transplantation is a promising treatment for advanced liver diseases, and adipose-derived mesenchymal stem cells are a hot topic following bone marrow mesenchymal stem cells. OBJECTIVE: To explore the therapeutic effect of adipose-derived mesenchymal stem cells transplantation via the hepatic artery on advanced liver diseases in rats. METHODS: Forty-five rats were randomized into three groups, 15 rats in each group: control group, model group and transplantation group. Rat models of liver cirrhosis were made in the latter two groups through subcutaneous injection of carbon tetrachloride. Then, 1 mL of CFSE-labeled adipose-derived mesenchymal stem cells was infused via the hepatic artery in the transplantation group, and the same volume of normal saline was infused in the model group. Control group had no treatment. Pathological changes, liver function and degree of hepatic fibrosis were observed in the three groups at 4 weeks after treatment. RESULTS AND CONCLUSION: After transplantation, green fluorescence-labeled adipose-derived mesenchymal stem cells were seen in the liver of rats. Hematoxylin-eosin staining and Masson staining showed unclear hepatic lobule structure in the model group with the formation of false lobules, cell cloudy swelling and loose, some degeneration and necrosis, and inflammatory cell infiltration; in the control group, there was nothing abnormal in the liver tissues of rats in the control group; in the transplantation group, the pathological changes of the rat liver were better than those in the model group, but worse than those in the control group. Compared with the model group, the level of serum albumin was higher in the control and transplantation group (P < 0.05), and the levels of bilirubin, aminotransferase and type IV collagen were lower in the control and transplantation group (P < 0.05). Thus, it can be seen that adipose-derived mesenchymal stem cell transplantation can improve liver function and reduce liver fibrosis in cirrhotic rats.      

经肝动脉途径兔自体骨髓干细胞移植治疗肝硬化

BACKGROUND:How to make more transplanted bone marrow stem cells stay and differentiate in the liver is an important issue, which is also crucial for treatment of liver cirrhosis via the hepatic artery. OBJECTIVE:To investigate the therapeutic effect of autologous bone marrow stem cell transplantation via the hepatic artery on liver cirrhosis. METHODS:Thirty New Zealand white rabbits were equivalently randomized into normal control, stem cell transplantation and model groups. Animal models of liver cirrhosis were made in the latter two groups. Then, model rabbits in the stem cell transplantation group were subjected to autologous bone marrow stem cell transplantation via the hepatic artery. Liver function of rabbits was detected in 1, 2, 4, 8, 10 weeks after cell transplantation, and pathological detection of the liver was performed in the 10th week. RESULTS AND CONCLUSION:At 10 weeks after cell transplantation, the liver function of the rabbits was improved significantly compared with the model group, including reduced activities of serum alanine aminotransferase, total bilirubin and aspartate aminotransferase, shortened activated partial thromboplastin time, and increased albumin level (P < 0.05). Pathological examination of the liver showed that the liver cells in the stem cell transplantation group were intact with no obvious edema and still had the structure of the pseudolobule, and compared with the model group, the degree of liver fibrosis was significantly reduced in the stem cell transplantation group. Our experimental results show that the transplantation of autologous bone marrow stem cells via the hepatic artery has a certain therapeutic effect on liver cirrhosis by increasing the body albumin content in a short time and improving the liver function.     

实验性自身免疫性肝炎的研究

本文通过 S-100肝抗原多次免疫同种 C57BL/6小鼠后,成功地建立了实验性自身免疫性肝炎的动物模型,并在此基础上进一步探讨了过继输注致敏脾淋巴细胞给正常同种小鼠后自身免疫性肝炎的发生情况.结果表明,导致过继输注后自身免疫性肝炎主要为 T 淋巴细胞,揭示了 T 淋巴细胞在自身免疫性肝炎发病中起着重要作用.另外,本文还就免疫抑制剂环孢素 A 对实验性自身免疫性肝炎的防治作用进行了探讨.组织学检查结果表明预防和治疗用药时均能减轻肝脏病理变化和/或减少自身免疫性肝炎的发生率.为临床治疗自身免疫性肝炎提供了实验室依据.     

脂肪干细胞在颗粒脂肪移植中的作用

背景:血管基质层细胞中含有大量的脂肪干细胞,有研究显示脂肪干细胞在移植过程中可能发挥着很重要的作用。目的:观察脂肪干细胞在颗粒脂肪移植中的作用。方法:选取10只雄性SPF级BALB/C小鼠,取出正常脂肪组织,提取动物腹部脂肪中的脂肪干细胞和颗粒脂肪,选取24只裸鼠作为移植受体,所有动物分为3个实验组,分别为对照组、颗粒脂肪移植组、混合移植组(脂肪干细胞和颗粒脂肪)。2个移植组分别将颗粒脂肪细胞悬液及脂肪干细胞和颗粒脂肪混匀后细胞悬液注射到小鼠腹背左右肩胛处;对照组注射等量的细胞基础培养液。4周后,分离血浆及取出移植物进行指标检测。结果与结论:(1)混合移植组能显著性的增加移植物的质量,降低移植脂肪的吸收率,相对于颗粒脂肪移植组差异有显著性意义(P<0.01);(2)移植后血浆中血管内皮细胞生长因子相对于对照组明显提升,其中混合移植组高于颗粒脂肪移植组(P<0.01);(3)颗粒脂肪移植组碱性成纤维细胞生长因子的含量明显低于相混合移植组;(4)混合移植组微血管密度显著高于颗粒脂肪移植组(P<0.01);(5)动物移植物中的细胞形态较单纯颗粒脂肪细胞完好;(6)混合移植组的脂肪油滴的数目明显多于颗粒脂肪移植组;(6)结果提示,脂肪干细胞能够显著性提高碱性成纤维细胞生长因子的表达,改善移植物的微循环,显著改善颗粒脂肪细胞的形态和功能。     

同基因造血干细胞移植延长同种异体小鼠皮肤移植物存活时间的实验研究

为了研究同基因造血干细胞移植诱导器官移植免疫耐受的可行性。建立小鼠异基因皮肤移植模型,术后2周给予FK506腹腔注射,3周起行全身照射及同基因骨髓移植,观察记录小鼠和移植物存活情况,以流式细胞检测受体GFP嵌合表达,混合淋巴细胞反应、迟发型超敏反应检测诱导耐受的特异性和效能。实验组小鼠移植物存活时间达(29.14±4.92)d,显著长于对照组(P<0.05);GFP在BMT后4周、6周嵌合程度达到82%、91%;实验组MLR、DTH结果与对照组差异显著,提示诱导耐受具有高度特异性和高效性。同基因造血干细胞移植联合免疫抑制剂治疗可以有效诱导小鼠皮肤移植的免疫耐受。     

异体脂肪源干细胞移植对大鼠的抗衰老作用

目的从筋膜学的角度设计观察脂肪源干细胞(ADSCs)异体移植对衰老模型大鼠体内自由基和免疫功能的影响,探索一种新的抗衰老方法。方法30只SD大鼠随机分成空白对照组(A组)、模型组(B组)和治疗组(C组)。B、C组大鼠注射D-半乳糖(D-gal)复制亚急性衰老模型。C组大鼠在造模8周后,经尾静脉输入体外扩增培养的脂肪源干细胞3×106个。治疗2周后,检测各组大鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、血清白细胞介素-2(IL-2)水平和脾脏指数。结果与空白对照组比较,模型组大鼠血清SOD、NO、IL-2水平及脾脏指数均显著性降低,血清MDA水平显著升高;移植ADSCs后,治疗组大鼠较模型组大鼠血清SOD、NO、IL-2水平及脾脏指数均有所提高,而MDA含量显著降低。结论异体移植ADSCs可有效增强大鼠机体清除自由基和抗氧化能力,提高机体免疫功能,从而延缓D-gal诱发的大鼠衰老。     

小鼠脂肪干细胞的免疫原性及移植安全性*

背景：多组实验证实脂肪干细胞体外能够大量扩增,经一定诱导条件作用后能够向3个胚层分化,并且能够加以一定的基因修饰。 目的：观察小鼠脂肪干细胞的免疫原性和经静脉移植后的安全性。 方法：体外分离培养小鼠脂肪干细胞,流式细胞仪鉴定细胞表面的免疫标记物;体外淋巴细胞增殖试验检测脂肪干细胞对淋巴细胞的活化能力;经小鼠尾静脉移植脂肪干细胞,观察细胞在体内对小鼠T、B淋巴细胞的刺激作用;仔细解剖移植后小鼠,观察细胞移植后的成瘤性。 结果与结论：脂肪干细胞在体外容易扩增培养,表达间质干细胞表面标记物;体外与淋巴细胞共培养时,不能有效刺激淋巴细胞增殖;经静脉移植后,不能激活机体细胞免疫反应,但是能够活化B淋巴细胞,激活机体体液免疫反应;细胞移植后未观察到肿瘤形成和组织畸变。提示脂肪干细胞总体免疫原性较低,移植后不会激活宿主细胞免疫系统;脂肪干细胞移植后无肿瘤样生长,安全性较好。     

同种异体移植骨髓间质干细胞治疗大鼠心梗后心室重构

目的： 观察骨髓间质干细胞（MSCs）移植对大鼠心梗后心室重构和心功能的影响，比较成年大鼠MSCs与乳鼠MSCs移植疗效，初步探讨同种异体移植的可行性。方法: 分别取大鼠和乳鼠的骨髓，体外分离、扩增培养MSCs，Brdu标记。在结扎冠脉后1-2 h 分别将大鼠MSCs和乳鼠MSCs分点注射到异体大鼠心脏梗死边缘区，6周后，采用超声心动图和解剖直测法获得大鼠心功能、心室重构和病理学资料。结果: 细胞移植组左室舒张末期内径和收缩末期内径短于、室壁厚于对照组，重量指数和心室腔都明显小于对照组。组织病理表现细胞移植组心梗区心肌数目多于、血管密度大于对照组，细胞外基质胶原的形成和血管周围胶原沉积均明显少于对照组，心梗区可见Brdu阳性细胞。但大鼠MSCs移植组和乳鼠MSCs移植组间无明显差异。结论: 同种异体骨髓间质干细胞可以在心梗区定植，减少胶原形成，促进心肌和血管生成，从而延缓心梗后心室重构，提高左室收缩和舒张功能。成年鼠干细胞移植与乳鼠干细胞移植具有相似的效果。     

肝干细胞移植治疗大鼠暴发性肝功能衰竭的实验研究

目的探索肝干细胞移植对暴发性肝功能衰竭大鼠的治疗效果。方法以二乙酰氨基芴(15mg/kgBW)联合2/3肝切除建立雄性大鼠肝干细胞增殖模型,以改进Seglen胶原酶原位灌注及Percoll密度梯度离心方法分离、纯化肝干细胞,经肝脏注射移植(4×106细胞)治疗由D-氨基半乳糖诱导的暴发性肝功能衰竭雌性大鼠,移植前及移植后24、48、72h及1周取血测定肝功能指标如血氨、ALT、TBiL,移植后1、2、4周取受体肝脏组织应用PCR方法进行性别决定因子检测。结果肝干细胞移植可延长暴发性肝功能衰竭大鼠的中位生存时间(P<0.05),移植后肝干细胞移植组大鼠血清ALT、TBiL及血氨水平明显下降,其测定值各时间点组间比较,治疗组明显低于对照组(P<0.01);肝脏病理损伤减轻,肝干细胞移植2周后雌性受体肝脏组织中性别决定因子呈阳性表达,且随时间延长而表达增强。结论肝干细胞移植可延长暴发性肝功能衰竭大鼠中位生存时间,改善肝功能及病理指标。     

同种异体脂肪干细胞门脉移植对大鼠纤维化肝脏的影响

目的: 研究同种异体脂肪干细胞肝内移植对大鼠纤维化肝脏的影响。方法: 从SD大鼠腹膜脂肪组织提取脂肪干细胞,纯化、培养并稳定传代。雄性SD大鼠48只,成功建立大鼠肝纤维化模型。实验分为对照组(n=14)、门静脉组(n=11)和尾静脉组(n=14)。后两组分别经门静脉、尾静脉注射同种异体移植脂肪干细胞,观察移植前后大鼠肝血流动力学变化,并比较门静脉组和尾静脉组的疗效差异。结果: 成功提取脂肪干细胞,纯化、培养并稳定传代。输注脂肪干细胞前后各组肝脏计算机断层扫描灌注指数显示,门静脉组肝脏血流灌注有明显改善,且以门静脉灌注量为主(P<0.05),尾静脉组仅有轻微改善。组织学肝硬化评分显示,门静脉组见肝纤维化、肝细胞脂肪变性、肝细胞变性坏死均明显改善(P<0.05);尾静脉组仅肝细胞脂肪变性有改善。免疫组化示门静脉组肝脏微血管密度较其它组明显减少(P<0.05)。结论: 同种异体脂肪干细胞移植能改善肝纤维化SD大鼠的肝脏血流灌注及病理学改变;门静脉移植途径较尾静脉途径疗效更显著。     

同种异体BMSCs、ADSCs移植后的抗原性差异

目的　探讨骨髓来源间充质干细胞（MSCs from bone marrow, BMSCs）与脂肪来源间充质干细胞(Adipose tissue-derived MSCs,ADSCs)体内移植后的抗原性差异。 方法 体外培养WKY大鼠BMSCs、ADSCs,经成骨诱导后植入wistar大鼠桡骨缺损区,分别于植入后1、2、4、8周进行缺损区HE染色,于1、2、4、8周免疫组化检测缺损区IL-2、TGF-β、TNF-α、CD4、CD8,采用ELISA法检测脾细胞培养液上清IL-2、TGF-β、TNF-α的含量。 结果 BMSCs、ADSCs移植术后1～2周有少量淋巴细胞、白细胞浸润,IL-2、TGF-β、TNF-α、CD4、CD8蛋白少量表达;二者比较差异无显著性。 结论 BMSCs、ADSCs体内移植后所致的抗原性无显著性差异。     

同基因与异基因胚胎肝干细胞移植治疗小鼠肝硬化

背景：胚胎肝干细胞移植免疫相关研究较少,同基因与异基因胚胎肝干细胞移植对小鼠肝硬化的治疗作用,目前尚不清楚。 目的：观察同种同基因与同种异基因胚胎肝干细胞移植对小鼠肝硬化的治疗作用,以及治疗过程中免疫排斥反应发生情况。 方法：采用Ⅳ型胶原酶消化法分离纯化BALB/c与C57BL/6胚胎肝干细胞。104只健康BALB/c小鼠随机分为4 组：正常对照组不予任何处理;肝硬化组、同种同基因移植组、同种异基因移植组腹腔注射四氯化碳石蜡油溶液复制肝硬化模型,16周后分别经其尾静脉注射生理盐水,等量同种同基因胚胎肝干细胞和同种异基因胚胎肝干细胞。在移植4周后比较各组受体小鼠存活情况、肝功能恢复情况、肝纤维化程度、免疫细胞(CD4⁺T、CD8⁺T、NK、NKT)数目及比值、肝脏病理学变化。 结果与结论：同种同基因移植组和同种异基因移植组生存率均为100%,与肝硬化组小鼠存活率67%相比差异有显著性意义(P < 0.05);各组肝功能和肝纤维化指标差异无显著性意义(P > 0.05)。各组免疫学指标比较差异无显著性意义(P > 0.05)。肝脏组织病理学显示肝组织修复：同种异基因移植组>同种同基因移植组>肝硬化组。因此,经尾静脉移植胚胎肝干细胞能提高肝硬化小鼠的生存率、减轻肝细胞坏死程度;同种同基因与同种异基因胚胎肝干细胞移植未发现免疫排斥,对小鼠肝硬化有一定的治疗作用。     

FXR通过调节促甲状腺素胚胎因子减轻Con A诱导的自身免疫性肝炎病变

 目的：观察法尼酯衍生物X受体（farnesoid X receptor,FXR)-促甲状腺素胚胎因子（thyrotropin embryonic factor,TEF）通路在自身免疫性肝炎模型小鼠肝损害中的作用,探讨FXR-TEF通路改善自身免疫性肝炎的部分可能机制。方法：检测FXR在伴刀豆球蛋白A (concanavalin A, Con A) 诱导的肝炎（Con A-induced hepatitis, CIH）小鼠肝脏的表达;检测FXR激活对TEF表达的影响;观察C57BL/6小鼠和鹅去氧胆酸（chenodeoxycholic acid,CDCA）激活FXR的CIH小鼠肝脏病理、肝脏酶学及炎症因子变化。结果：FXR在CIH小鼠中低表达;CDCA激活FXR的C57BL/6小鼠TEF表达上调;FXR被激活的CIH小鼠的肝损害较轻,FXR激活可减轻肝脏炎症因子释放。结论：CDCA激活FXR能减轻CIH引起的肝功能损害和炎症反应。FXR激活使TEF上调。FXR可能是自身免疫性肝炎的保护因素,其保护作用可能是通过TEF来实现的。激活FXR可能成为治疗自身免疫性肝炎的一个途径。     

Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis

Concanavalin A (Con A)‐induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c⁺ I‐A^low B220⁺); however, conventional DC were CD11c⁺ I‐A^high B220^–. At an early stage (3–6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12–24 h) in parallel with hepatic failure. The hepatic CD11c⁺ DC population contained many CD11b^‐ cells, while the majority of splenic CD11c⁺ DC were CD11b⁺. After Con A administration, the proportion of I‐A⁺ and CD11b⁺ cells within the CD11c⁺ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c⁺ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)‐12 and IL‐2, rather than modulating effector cell function.     

脂肪间充质干细胞对野百合碱诱发的肺动脉高压大鼠肺动脉钙离子通道的影响

 目的：探讨脂肪间充质干细胞(adipose tissue-derived mesenchymal stem cells,ADMSCs)移植对野百合碱（monocrotaline,MCT）诱发的肺动脉高压（pulmonary arterial hypertension,PAH）大鼠肺动脉钙离子通道的影响。方法：胶原酶消化法分离培养ADMSCs。雄性SD大鼠24只,分为正常对照组（Ctr组）、PAH组和ADMSCs组,每组8只。右心导管法测定大鼠的平均肺动脉压(MPAP);称重法测右心室肥厚指数（RVHI）;分别用RT-PCR及Western blotting法测定大鼠肺动脉干电压门控性钙离子通道α1c亚基（CaVα1c）肌浆/内质网Ca2+ ATP酶2a（SERCA-2a）、三磷酸肌醇受体1（IP3R-1）、瞬时受体电位通道1（TRPC1）和TRPC6 mRNA和蛋白的表达水平。结果：（1）MCT注射4周后,与Ctr组相比, PAH组大鼠MPAP和RVHI均显著升高（P<0.05）;ADMSCs移植2周后,与PAH组相比,ADMSCs组MPAP和RVHI均明显降低（P<0.05）。（2）与Ctr组相比,PAH组大鼠肺动脉CaVα1c、TRPC1和TRPC6 mRNA及蛋白表达水平均明显增强（P<0.05）,SERCA-2a 和IP3R-1 mRNA及蛋白表达水平均明显降低（P<0.05）;与PAH组相比,ADMSCs组CaVα1c、TRPC1和TRPC6的表达均明显降低（P<0.05）,SERCA-2a 和IP3R-1的表达均明显增强（P<0.05）。结论：ADMSCs能有效地降低MCT诱发的PAH大鼠的肺动脉压力,减轻右心室肥厚。ADMSCs降低肺动脉压力可能与钙离子通道变化有关。     

HO-1高表达对脂肪干细胞在低氧无血清条件下的保护作用及机制

 目的:探讨诱导内源性血红素氧合酶-1（HO-1）表达对脂肪干细胞（ADSCs）在低氧无血清条件下的保护作用及其可能的分子机制。方法: 分离培养SD大鼠脂肪干细胞进行低氧无血清处理,DAPI染色检测细胞凋亡率;Western blotting 法分析HO-1、NLRP3 、凋亡相关斑点样蛋白 (ASC)和cleaved caspase-1的蛋白表达;ELISA 法测定培养上清液中白细胞介素-1β (IL-1β) 的水平;采用 DCFH-DA 荧光探针检测细胞内活性氧 (ROS) 的水平。结果: 钴原卟啉诱导ADSCs HO-1蛋白呈剂量依赖性表达,以20 μmol/L最为显著;诱导内源性HO-1的表达明显抑制ADSCs在低氧无血清条件下的细胞凋亡率和NLRP3、ASC、cleaved caspase-1的蛋白表达,并减少细胞内ROS和上清液IL-1β的水平;而这种保护效应可被同时给予的HO-1抑制剂锌原卟啉所逆转。结论: 诱导内源性HO-1的表达可能通过抑制NLRP3炎症小体的激活以及减少IL-1β的分泌,对低氧无血清条件下ADSCs发挥保护作用。     

嗅鞘细胞移植对大鼠实验性自身免疫性脑脊髓炎的影响

目的:探索嗅鞘细胞移植实验性自身免疫性脑脊髓炎(EAE)大鼠的移植途径、可行的移植时间窗,移植后的迁移特性以及发挥保护作用的可能机制。方法:分别采用豚鼠脊髓匀浆(GPSCH)与MOGIgd融合蛋白免疫Lewis大鼠,制作EAE模型;每组发病大鼠分别归入:MOG组和GPSCH组。MOG组分为:OECs空白对照组(MOG0组)4只、OECs尾静脉移植组(MOG1组)7只、OECs侧脑室移植组(MOG2组)4只;GPSCH组分为:OECs空白对照组(GPSCH0组)4只、OECs尾静脉移植组(GPSCH1组)4只。发病高峰期,按照实验分组,分别采用立体定向侧脑室细胞移植和尾静脉细胞移植,观察移植后大鼠的临床症状;移植后2周观察OECs在大鼠体内的分布情况及组织病理学方面的缓解情况。结果:OECs分别经尾静脉、侧脑室移植后,EAE大鼠症状改善,与空白对照组神经功能评分峰差值比较有显著差异(F=18.470,P0.01;t=-7.147,P0.01),MOG1组和MOG2组评分峰差值间无显著差异(P0.05);Hoechst33342示踪证实了OECs能在大鼠体内存活及强大的迁移能力;OECs经尾静脉移植后,可以透过破坏的血脑屏障进入脑内,分布于软脑膜和病灶周围;经侧脑室移植的嗅鞘细胞,向病灶局部广泛迁移;组织病理学评分(HE染色和Luxol fast blue髓鞘染色),移植组与未移植组间无显著差异(P0.05),2种途径移植组间亦无显著差异(P0.05)。结论:纯化培养的成年大鼠嗅球嗅鞘细胞分别经尾静脉和侧脑室移植EAE大鼠,均可缓解发病大鼠的症状。     

Treatment of autoimmune diseases in MRL/lpr mice by allogenic bone marrow transplantation plus adult thymus transplantation

CD1d-restricted invariant natural killer T (iNK T) cells activated by their experimental ligand alpha-galactosylceramide (alpha-GC) can produce both T helper 1 (Th1) and Th2 cytokines and display regulatory functions. Recent studies identified CD4(+) and CD4(-) CD8(-) double-negative (DN) iNK T cells as the two major components of the human population and suggest that they display a Th2 and a Th1 profile, respectively. We compared the Th2-promoting activity of freshly isolated human CD4(+) and DN iNK T cells in terms of their capacity to induce Ig production by autologous B cells. Secretion of IgG and IgE but not IgM was enhanced by the CD4(+) T cell subset (including iNK T cells) but not by its DN counterpart. iNK T cells were directly responsible for this pro-Th2 effect, as demonstrated by the requirement for both alpha-GC stimulation and CD1d presentation, as well as by its disappearance upon iNK T cell depletion. Interaction with iNK T cells led to progressive accumulation of isotype-switched and activated B cells. Myeloid dendritic cells (DC) completely block the induction of Ig production in co-culture. This dominant inhibitory effect of myeloid DC was concomitant with a specific loss of interleukin (IL)-4 production by CD4(+) iNK T but not by conventional T cells. These data support the conclusion that, conversely to the interferon (IFN)-gamma-producing DN human iNK T cell population, interleukin (IL)-4-producing CD4(+) iNK T cells can activate and help B cells to produce both IgG and IgE through a CD1d-dependent mechanism, in keeping with a functional Th1/Th2 dichotomy between these subsets.     

间充质干细胞株C3H10移植治疗小鼠实验性变态反应性脑脊髓炎的实验研究

观察鼠源性间充质干细胞株C3H10移植对实验性变态反应性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)模型小鼠疾病进程的影响,为研究多发性硬化症(multiple sclerosis,MS)等自身免疫性疾病的治疗提供实验基础。采用MOG35-55抗原与完全弗氏佐剂(IFA)免疫C57BL/6雌性小鼠制作EAE模型;24只小鼠分成三组,即未干预对照组、C3H10细胞移植组和正常对照组。通过HE染色,Fast-blue染色观察小鼠脑和脊髓的病理学改变,结合神经功能评分和体重测量的方法观察C3H10细胞移植对EAE小鼠的影响。结果:(1)动物行为学的改变:免疫后第10天开始,未干预对照组小鼠陆续出现EAE临床症状,第14至第18天达到发病高峰,平均神经功能评分为2.3±0.36(P<0.05),持续评分30d;C3H10细胞移植组小鼠有1只14 d和18 d神经功能评分为1分,正常对照组小鼠一直未出现临床症状(0分),持续观察30 d;(2)未干预对照组小鼠体重呈逐渐下降,第14天体重约(918.93±2.12)g,第22天约(18.65±2.04)g;C3H10细胞移植组小鼠体重有上升趋势,于造模后第14天称得体重为(18.7±0.93)g,造模后22 d小鼠体重保持在(19.26±0.58)g,两组相比具有统计学差异(P<0.05);(3)病理学改变:未干预对照组小鼠脑和脊髓小血管周围炎细胞浸润,呈袖套状或脱髓鞘改变,而C3H10细胞移植组和正常对照组小鼠未出现明显的脑和脊髓小血管炎症病理变化。小鼠间充质干细胞株C3H10移植于EAE小鼠可明显减少并延缓EAE发病,呈现一定的治疗作用。