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。     

干细胞生长因子和粒细胞集落刺激因子与心肌梗死大鼠体内骨髓间充质干细胞的迁移

背景：外周静脉移植间充质干细胞只有1%~5%的移植细胞能归巢到心肌梗死区域。 目的：观察干细胞生长因子、粒细胞集落刺激因子对骨髓间充质干细胞归巢的影响。 方法：采用贴壁培养法分离培养SD大鼠骨髓间充质干细胞,取传至3~5代细胞。建立SD大鼠急性心肌梗死模型,干细胞生长因子组、粒细胞集落刺激因子组、干细胞生长因子+粒细胞集落刺激因子组在骨髓间充质干细胞移植前3 d和移植后3 d单独或混合皮下注射干细胞生长因子、粒细胞集落刺激因子,骨髓间充质干细胞组不注射细胞因子。 结果与结论：荧光显微镜下观察,骨髓间充质干细胞迁移至心肌梗死组织,骨髓间充质干细胞组、干细胞生长因子组、粒细胞集落刺激因子组迁移至心肌梗死区的骨髓间充质干细胞数量没有明显的区别(P > 0.05),干细胞生长因子+粒细胞集落刺激因子组的骨髓间充质干细胞数量明显高于其他3组(P < 0.05)。免疫荧光组织化学显示,植入的部分骨髓间充质干细胞表达心肌特异蛋白cTnI。结果说明干细胞生长因子和粒细胞集落刺激因子两种细胞因子联合应用可以促进骨髓间充质干细胞归巢至心肌梗死区域,在体内微环境的诱导下,骨髓间充质干细胞能够转化为心肌样细胞。     

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：     

外源性硫化氢预处理骨髓间充质干细胞移植治疗大鼠心肌梗死

背景：骨髓间充质干细胞移植可促进心肌修复,治疗心肌梗死,但移植后细胞存活率低等原因制约了其应用与发展。 目的：探讨硫化氢预处理对骨髓间充质干细胞移植治疗心肌梗死效果的影响。 方法：从(100±20) g SD大鼠中分离培养骨髓间充质干细胞,第4代时按实验分组处理,移植前2 h给予DAPI标记。将50只体质量(200±20) g雄性SD大鼠分为心肌梗死组和假手术组,心肌梗死组结扎冠状动脉前降支建立心肌梗死模型,假手术组只穿线不结扎,每组10只。模型建立24 h后,分组在梗死心肌周围选择4个点,分别注射生理盐水、骨髓间充质干细胞、硫化氢预处理骨髓间充质干细胞及硫化氢。细胞移植4周后用超声心动图检测心功能指标,Masson染色测定梗死交界区胶原。 结果与结论：生理盐水组大鼠心肌纤维化严重,梗死区域无心肌组织再生;外源性硫化氢处理后的骨髓间充质干细胞移植组比单用硫化氢或者骨髓间充质干细胞组心肌纤维化程度轻,胶原组织中可见较多心肌细胞再生。硫化氢预处理骨髓间充质干细胞组左室射血分数、左室短轴缩短率显著高于硫化氢组及骨髓间充质干细胞组(P < 0.05)。提示硫化氢预处理骨髓间充质干细胞可提高移植后的细胞存活率,改善梗死后心功能,其作用优于单用硫化氢或者骨髓间充质干细胞。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：     

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     

银杏达莫注射液联合骨髓间充质干细胞移植改善脑梗死后的神经功能

背景：通过细胞移植重建损伤脑组织成为治疗脑梗死的新途径,骨髓间充质干细胞成为近年来细胞移植治疗领域的研究热点。 目的：探讨银杏达莫注射液联合骨髓间充质干细胞移植对脑梗死大鼠神经功能的改善作用及相关机制。 方法：利用线栓法制作大鼠大脑中动脉闭塞模型,建模成功后60只SD大鼠随机分为对照组、细胞移植组及联合组。对照组尾静脉注射PBS、细胞移植组尾静脉注射2.5×109 L-1的骨髓间充质干细胞悬液、联合组尾静脉注射2.5×109 L-1的骨髓间充质干细胞悬液和银杏达莫2 mL/kg,1次/d,连续注射5 d。于移植后的1,3 d及1,2 周进行mNSS行为学评分,以观察大鼠神经功能缺损状况。移植后2周RT-PCR检测脑组织中脑源性神经生长因子、生长相关蛋白43基因表达变化,TUNEL法检测细胞凋亡情况,免疫组化法检测BrdU阳性细胞数。 结果与结论：移植后的1,3 d各组大鼠神经功能缺损评分差异无显著性意义(P > 0.05),在移植后1,2周,联合组神经功能缺损评分低于细胞移植组及对照组(P < 0.05);移植后2周,联合组脑源性神经生长因子、生长相关蛋白43 mRNA表达明显高于细胞移植组及对照组(P < 0.05),联合组凋亡细胞数目明显少于细胞移植组及对照组(P < 0.05),联合组BrdU阳性细胞数量明显多于细胞移植组及对照组(P < 0.05)。结果表明骨髓间充质干细胞联合银杏达莫干预能促进脑梗死组织脑源性神经生长因子、生长相关蛋白43 mRNA的表达,抑制细胞凋亡,改善大鼠神经功能。  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      

吡格列酮联合骨髓间充质干细胞移植治疗改善大鼠心肌梗死后的心功能

背景：前期研究发现骨髓间充质干细胞移植能够改善心肌梗死大鼠的心功能,但整体效果并不太理想。 目的：拟采用PPAR-γ激动剂吡格列酮联合骨髓间充质干细胞移植治疗以进一步改善心肌梗死大鼠的心功能并探讨相关机制。 方法：开胸结扎20只SD大鼠左前降支冠状动脉并随机分为2组：骨髓间充质干细胞组和骨髓间充质干细胞+吡格列酮组。2周后在局部梗死心肌内注射PKH26标记的由PBS悬浮的骨髓间充质干细胞,联合治疗组在注射骨髓间充质干细胞后予以吡格列酮3 mg/(kg•d)连续灌胃2周。细胞移植后2周进行超声心动图检测,免疫荧光染色、Western blot、qRT-PCR检测左心室心肌组织不同区域PPAR-γ、TGF-β1/SMAD通路相关因子和Cx43的表达情况。 结果与结论：两组大鼠基础心功能参数无明显差异性。细胞移植2周后,骨髓间充质干细胞+吡格列酮组左室舒张末径、左室收缩末径明显减小,左室射血分数明显增高;左心室心肌组织不同区域PPAR-γ和Cx43的表达量显著增加;TGF-β1、SMAD2、SMAD3在梗死区和梗死边缘区表达明显下降。以上结果提示PPAR-γ激动剂吡格列酮干预能够增强骨髓间充质干细胞移植对心功能的改善作用,其机制可能与PPAR-γ抑制TGF-β1/SMAD通路进而提高Cx43的表达有关。  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     

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：     

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，...     

Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances

The first, to our knowledge, in-vivo broadband spectroscopic characterization of breast tissue using different interfiber distances as well as transmittance measurements is presented. Absorption and scattering properties are measured on six healthy subjects, using time-resolved diffuse spectroscopy and an inverse model based on the diffusion equation. Wavelength-tunable picosecond-pulse lasers and time-correlated single-photon counting detection are employed, enabling fully spectroscopic measurements in the range 610 to 1040 nm. Characterization of the absorption and reduced scattering coefficients of breast tissue is made with the aim of investigating individual variations, as well as variations due to different measurement geometries. Diffuse reflectance measurements at different interfiber distances (2, 3, and 4 cm) are performed, as well as measurements in transmittance mode, meaning that different sampling volumes are involved. The results show a large variation in the absorption and scattering properties depending on the subject, correlating mainly with the water versus lipid content of the breast. Intrasubject variations, due to different interfiber distances or transmittance modes, correlate with the known structures of the breast, but these variations are small compared to the subject-to-subject variation. The intrasubject variations are larger for the scattering data than the absorption data; this is consistent with different spatial localization of the measurements of these parameters, which is explained by the photon migration theory.     

Chemical and functional analysis of MHC class II-restricted T cell epitopes.

Various aspects of antigen degradation and presentation are reviewed, in particular with respect to fragmentation of native vs. denatured proteins, different enzymatic machinery present in different cells and individuals, characterization of epitopes and their persistence on antigen-presenting cells as well as their capacity to interact with different MHC class II molecules. Finally, the structure of antigenic peptides is discussed.     

基于近似熵的思维脑电信号分类研究

采用近似熵(approximate entropy，Apen)作为脑电信号的特征参数对不同思维作业脑电信号进行了分类研究，并对近似熵算法中参数的选择以及互近似熵在思维脑电分类的应用进行了讨探。研究结果表明，近似熵特征在思维作业脑电信号的分类中取得了较好的应用效果。近似熵作为EEG的信号特征为提高思维作业脑电信号的分类正确率提供了一种新的途径，在基于思维作业BCI的应用中具有重要的实用价值。     

New measurements to compare soft tissue anchoring systems in pelvic floor surgery

Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment.     

The macrophage in tuberculosis: sinner or saint? The T cell decides

Immunity to intracellular bacteria including Mycobacterium tuberculosis crucially depends on intricate interactions between T lymphocytes and macrophages. Before contact with T lymphocytes macrophages serve as habitat for M. tuberculosis organisms; after activation by T cells they become major effectors against these pathogens. T cells comprise different subsets which express different functional activities. This paper describes evidence that different T cell subsets (CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells) as well as different T cell functions (interleukin secretion and target cell lysis) contribute to immunity against tuberculosis.     

特异性CTL胞毒作用与HLA型别关系探讨

目的：探讨特异性CTL胞毒作用与靶细胞的HLA型别关系。方法：本实验以特定HLA型别，EB病毒转化的B淋巴母细胞（EBV－LCL）与同种异体单个核细胞（PBMC）混合培养，激活同种抗原特异性细胞性T细胞（CTL），观察其对携带不同HLA型别的EBV－LCL靶细胞的杀伤活性。结果：用EBV－LCL1致敏的效应细胞1对EBV－LCL2的杀伤效应比对EBV－LCL3强，用EBV－LCL2致敏的效应细胞2对EBV－LCL1的杀伤效应比对EBV－LCL3强，用EBV－LCL3致敏的效应细胞3对EBV－LCL1，2几乎无杀伤效应。结论：特异性CTL对不同HLA型别的靶细胞的胞毒作用存在差异，这不仅仅与HLA型别关联，而可能取决于抗原肽与MHC所组成的抗原综合信息。     

Characterization of adenovirus hexons by their epitope composition

Summary For the investigation of epitope composition of different adenovirus hexon types sixty-one mouse ascitic fluids containing monoclonal antibodies (MAbs) developed in three different panels were used. The distinction and marking of the different epitopes recognized by the MAbs were carried out by the determination of the composite cross-reactivity pattern, the titer and the correlation coefficient of all the 61 MAbs with 21 different hexon types representing all the six human subgenera, as well as different bovine and simian adenoviruses. The distinct epitopes were marked by two numbers refering the homologous hexon type to which the MAbs were directed and the serial number of the epitope specified by the different members of the given panel of the MAbs. The three panels of MAbs recognized 22 epitopes on the 21 hexon types among them a genus and three type specific ones and 18 different bi- and multilateral intertype (IT) specific epitopes that grouped adenoviruses within the genus, independently from the subgenus they belong to. Considering that the type specific epitope could be present only on the homologous hexon type, the largest number of the different epitopes distinguishable by the MAbs used could be 20 on the homologous hexon and 19 on the heterologous ones. It was found that the total number of IT specific epitopes on the hexons varied between 2 and 18. The distribution of the distinct specific epitopes on the different hexon types was different, as expected. The antigenic structure of the individual hexon types were characterized by the determination of their IT specific epitope spectrum. By pairwise analysis ten human hexon types formed three epitope clusters (types 4 and 19; types 8, 9, 9/13 and 10; as well as all types of subgenus C) showing identical epitope spectra. No clustering was found with human type 7, 12, 13, 18, 26, 27, 35 and 41, as well as with bovine and simian adenovirus hexons studied. However, they displayed a closer or looser antigenic relationship among each other and to members of the epitope clusters. The degree of antigenic relationship could be expressed by the similarity/dissimilarity percentage calculated from the number of the identical and different epitopes present on any two given hexon types.     

Behavioral patterns proceeding from liver thermoreceptors

Subdiaphragmatic denervated, liver heated rats eat as much and as long as subdiaphragmatic denervated, non-heated rats. This points to vagus and/or splanchnic nerve afferentation from hepatic thermoreceptors. Left abdomen heated rats eat and drink as much as left abdomen non-heated rats. Since however they show some different behavior patterns, the intervention of other nerve fibers other than vagal and/or splanchnic fibers should be acknowledged in order to account for the different behavior pattern.     

Do parents respond in different ways when children feel different emotions? The emotional context of parenting

When children experience emotions, do they view their primary caregiver as reacting in a different manner depending on the children's different emotions? Parental socialization of negative emotions and child psychopathology were examined among 161 inner city youth ages 11-14 years. These early adolescents were more likely to perceive their parents as responding in a different manner to different emotions than responding in the same way to different emotions. In addition, we asked if emotion-specific socialization strategies tell us more about child psychopathology than global socialization strategies do. Exploratory analyses suggest that a mixture of both emotion-specific and global socialization strategies may best predict child psychopathology. It remains important to clarify the emotional context of socialization strategies.