PDF(Pubmed)
Abstract：
UNASSIGNED: The lack of regenerative capacity of the central nervous system is one of the major challenges nowadays. The knowledge of guidance cues that trigger differentiation, proliferation, and migration of neural stem and progenitor cells is one key element in regenerative medicine. The extracellular matrix protein tenascin-C (Tnc) is a promising candidate to regulate cell fate due to its expression in the developing central nervous system and in the adult neural stem cell niches. Of special interest are the alternatively spliced fibronectin type III (FnIII) domains of Tnc whose combinatorial diversity could theoretically generate up to 64 isoforms in the mouse. A total of 27 isoforms have already been discovered in the developing brain, among others the domain combinations A1D, CD, and A124BCD.
UNASSIGNED: In the present study, these domains as well as the combination of the constitutively expressed FnIII domains 7 and 8 (78) were expressed in Chinese hamster ovary cells as pseudo-antibodies fused to the Fc-fragment of a human immunoglobulin G antibody. The fusion proteins were presented to primary mouse neural stem/progenitor cells (NSPCs) grown as neurospheres, either as coated culture substrates or as soluble additives in vitro. The influence of the domains on the differentiation, proliferation and migration of NSPCs was analyzed.
UNASSIGNED: We observed that the domain combination A124BCD promoted the differentiation of neurons and oligodendrocytes, whereas the domain A1D supported astrocyte differentiation. The constitutively expressed domain 78 had a proliferation and migration stimulating impact. Moreover, most effects were seen only in one of the presentation modes but not in both, suggesting different effects of the Tnc domains in two- and three-dimensional cultures.
UNASSIGNED: This knowledge about the different effect of the Tnc domains might be used to create artificial three-dimensional environments for cell transplantation. Hydrogels spiked with Tnc-domains might represent a promising tool in regenerative medicine.
UNASSIGNED: In the present study, these domains as well as the combination of the constitutively expressed FnIII domains 7 and 8 (78) were expressed in Chinese hamster ovary cells as pseudo-antibodies fused to the Fc-fragment of a human immunoglobulin G antibody. The fusion proteins were presented to primary mouse neural stem/progenitor cells (NSPCs) grown as neurospheres, either as coated culture substrates or as soluble additives in vitro. The influence of the domains on the differentiation, proliferation and migration of NSPCs was analyzed.
UNASSIGNED: We observed that the domain combination A124BCD promoted the differentiation of neurons and oligodendrocytes, whereas the domain A1D supported astrocyte differentiation. The constitutively expressed domain 78 had a proliferation and migration stimulating impact. Moreover, most effects were seen only in one of the presentation modes but not in both, suggesting different effects of the Tnc domains in two- and three-dimensional cultures.
UNASSIGNED: This knowledge about the different effect of the Tnc domains might be used to create artificial three-dimensional environments for cell transplantation. Hydrogels spiked with Tnc-domains might represent a promising tool in regenerative medicine.
摘要：
■中枢神经系统缺乏再生能力是当今的主要挑战之一。引导线索的知识，触发分化，扩散,神经干细胞和祖细胞的迁移是再生医学的关键要素之一。细胞外基质蛋白tenascin-C（Tnc）由于其在发育中的中枢神经系统和成年神经干细胞壁龛中的表达，因此是调节细胞命运的有希望的候选者。特别感兴趣的是Tnc的选择性剪接的纤连蛋白III型（FnIII）结构域，其组合多样性理论上可以在小鼠中产生多达64种同种型。在发育中的大脑中已经发现了总共27种亚型，在其他领域组合A1D中，CD,A124BCD
■在本研究中，这些结构域以及组成型表达的FnIII结构域7和8(78)的组合在中国仓鼠卵巢细胞中表达为与人免疫球蛋白G抗体的Fc片段融合的假抗体。将融合蛋白呈递至生长为神经球的原代小鼠神经干/祖细胞（NSPCs），作为包被的培养基质或作为体外可溶性添加剂。域对分化的影响，分析了NSPCs的增殖和迁移。
■我们观察到结构域组合A124BCD促进了神经元和少突胶质细胞的分化，而结构域A1D支持星形胶质细胞分化。组成型表达的结构域78具有增殖和迁移刺激作用。此外，大多数效果只在一种演示模式中看到，而不是在两种模式中看到，表明Tnc域在二维和三维培养中的不同作用。
■关于Tnc域的不同作用的这种知识可能用于创建用于细胞移植的人造三维环境。掺有Tnc结构域的水凝胶可能代表再生医学中的有前途的工具。
■在本研究中，这些结构域以及组成型表达的FnIII结构域7和8(78)的组合在中国仓鼠卵巢细胞中表达为与人免疫球蛋白G抗体的Fc片段融合的假抗体。将融合蛋白呈递至生长为神经球的原代小鼠神经干/祖细胞（NSPCs），作为包被的培养基质或作为体外可溶性添加剂。域对分化的影响，分析了NSPCs的增殖和迁移。
■我们观察到结构域组合A124BCD促进了神经元和少突胶质细胞的分化，而结构域A1D支持星形胶质细胞分化。组成型表达的结构域78具有增殖和迁移刺激作用。此外，大多数效果只在一种演示模式中看到，而不是在两种模式中看到，表明Tnc域在二维和三维培养中的不同作用。
■关于Tnc域的不同作用的这种知识可能用于创建用于细胞移植的人造三维环境。掺有Tnc结构域的水凝胶可能代表再生医学中的有前途的工具。
