Reactive astrocytes: cellular and molecular cues to biological function

For several decades, the reactive gliosis that occurs after an injury to the CNS has been considered one of the major impediments to axonal regeneration. Nevertheless, recent studies have suggested that in certain conditions, reactive astrocytes may provide a permissive substratum to support axonal regrowth. The important criteria, allowing for the distinction between permissive and non-permissive gliosis, are the ultrastructural 3D organization of the scar and more importantly the recognition molecules expressed by reactive astrocytes. Reactive astrocytes express surface molecules and produce various neurotrophic factors and cytokines. The latter in turn might modulate the production of recognition molecules by reactive astrocytes, allowing them to support post-lesional axonal regrowth.  Although numerous recent articles have focused on cytokines and cell adhesion molecules, scant attention has been paid to reactive astrocytes. Reactive astrocytes should be considered a key element, like neurons, of a dynamic environment, thus forming with neurons a functional unit involved in homeostasis, plasticity and neurotransmission.  Attempts are in progress to identify molecular markers for reactive astrocytes.     

PDX-1蛋白对棕榈酸诱导的大鼠胰岛凋亡的保护作用

目的探讨PDX-1蛋白对棕榈酸诱导的大鼠胰岛凋亡的保护作用。方法PDX-1基因克隆及表达质粒的构建,PDX-1蛋白的表达、纯化和鉴定,PDX-1蛋白保护棕榈酸引起的胰岛细胞凋亡的研究。结果PDX-1蛋白可以延缓胰岛细胞的自然凋亡过程,保护其三维形态;可以降低处理后的胰岛Caspase-3活性,同时可以增加葡萄糖刺激胰岛素释放,PDX-1蛋白干预后的棕榈酸组（1.560±0.074）uIU/mL,与对照组（1.426±0.056）uIU/mL相比有显著差异（P〈0.05）。结论表明PDX-1蛋白可以减少棕榈酸诱导的胰岛凋亡,保护β细胞功能。     

大鼠脊髓损伤后巢蛋白在脊髓组织中的表达

目的探讨大鼠脊髓损伤后巢蛋白(nestin)的表达规律及其意义。方法30只Wister成年大鼠,随机分为正常对照组(A组)、损伤组(B组)。采用Allen打击模型(25g·cm),在T10段造成急性脊髓损伤,于损伤后1d、3d、1周、4周、8周进行取材,对距离损伤中心5mm处脊髓进行nestin免疫组化检测。应用图像分析软件进行nestin阳性区域面积侧算。结果A组脊髓室管膜细胞只可见极少数细胞胞浆内nestin表达,白质中几乎无表达。B组中nestin于损伤后24h表达于室管膜以及软膜,灰质和白质亦有少量表达,1周达到高峰(P<0.05),4周明显下降,8周时很少或几乎无表达。结论脊髓组织的许多部位可能存在具有分化和更新潜能的祖细胞,脊髓损伤后这些细胞被激活,在功能恢复中可能发挥着重要的作用。     

神经再生素对皮层细胞基因表达影响的基因芯片研究

目的：采用基因芯片技术,观察神经再生素对体外培养的胚鼠大脑皮质细胞基因表达的影响。方法：取ICR胚鼠（15d)大脑皮层细胞,无血清培养。实验组加入神经再生素（2μg/ml）,对照组加入等量基础培养液。培养6h后,抽提实验组和对照组皮层细胞总RNA,经反转录分别用Cy5、Cy3荧光标记成cDNA探针。将荧光标记的cDNA与MGEC－40s基因表达谱芯片杂交,芯片扫描、数据处理。结果：实验组与对照组大脑皮质细胞出现64条差异性表达的基因。呈现上调的基因有：钙调素结合蛋白、锌指蛋白激酶、核糖体蛋白等基因;下调基因有：抑制细胞分裂因子等基因。结论：神经再生素可作用于体外培养的胚鼠大脑皮层细胞,从基因调控水平促进脑细胞生长。     

伊里扎诺夫技术修复兔胫骨骨缺损成骨机制的研究

目的探讨截骨推移区骨愈合的组织学特点和新骨形成规律。方法取青紫蓝兔24只,建立胫骨大段骨缺损模型,在近干骺端截骨。分别于截骨后第1、2、4、6、8、10周各处死4只兔,在近干骺端的分离区取材进行组织学观察。结果截骨后第1周出现血肿机化,第4周出现膜内成骨和软骨内成骨,第6周推移区大部分被骨性骨痂取代,第8周开始改建。结论推移区存在膜内成骨和软骨内成骨2种方式,以膜内成骨为主。     

Follistatin antagonizes Activin signaling and acts with Notum to direct planarian head regeneration

Animals establish their body plans in embryogenesis, but only a few animals can recapitulate this signaling milieu for regeneration after injury. In planarians, a pluripotent stem cell population and perpetual signaling of polarity axes collaborate to direct a steady replacement of cells during homeostasis and to power robust regeneration after even severe injuries. Several studies have documented the roles of conserved signaling pathways in maintaining and resetting axial polarity in planarians, but it is unclear how planarians reestablish polarity signaling centers after injury and whether these centers serve to influence identity decisions of stem cell progeny during their differentiation. Here we find that a planarian Follistatin homolog directs regeneration of anterior identity by opposing an Activin/ActR-1/Smad2/3 signaling pathway. Follistatin and Notum, a Wnt inhibitor, are mutually required to reestablish an anterior signaling center that expresses both cues. Furthermore, we show that the direction of cells down particular differentiation paths requires regeneration of this anterior signaling center. Just as its amphibian counterpart in the organizer signals body plan and cell fate during embryogenesis, planarian Follistatin promotes reestablishment of anterior polarity during regeneration and influences specification of cell types in the head and beyond.     

Novel regenerative strategies to enhance periodontal therapy outcome

Background: Chronic periodontitis is a widely prevalent inflammatory condition of the supporting tissues of the teeth and is characterized by loss of teeth with an associated risk of systemic complications. Regenerative therapies such as guided tissue and bone regeneration form an important armamentarium in periodontics with a high degree of outcome predictability in certain ideal clinical scenarios. Objective/methods: This review elaborates novel tissue regenerative treatment modalities based on sound understanding of developmental biology, tissue engineering, inflammation and wound healing. We focus on the role of biological mediators such as growth factors, gene-based therapy, cell therapy and pro-resolution lipid mediators in the regeneration of lost bone or periodontium. Results/conclusions: These therapies have the potential to regenerate both periodontium and bone, aiding in the treatment of even clinically challenging cases.     

成人胰腺干细胞分离及转分化为胰岛的研究

目的 通过对成人胰腺干细胞分离和转分化为胰岛过程的研究以便更进一步了解及改进胰腺干细胞分离、培养、鉴定方法。方法 成人胰腺组织以胶原酶消化，密度梯度离心法获得纯化的胰腺外分泌细胞、导管上皮细胞和胰岛。导管上皮细胞在体外共培养27d，观察细胞形态学变化及干细胞特异性转录基因PDX—1，CK—19蛋白等的表达。结果 上述方法可获得大量胰腺导管上皮细胞。体外培养第1天即可见PDX—1，CK—19阳性细胞，胰腺导管上皮细胞迅速分裂增殖并转变为有分化能力的干细胞继而转分化为三维结构的胰岛细胞。培养27d后，平均每克胰腺组织可生成760个胰岛。结论 用改进的方法可获得大量成人胰腺导管上皮细胞，并可在体外转分化为大量具有内分泌功能的胰岛，可能为克服胰岛移植的供体短缺提供一条新途径。