Glotzbach Kristin, Stamm Nils, Weberskirch Ralf, Faissner Andreas
Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum, Bochum, Germany.
Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany.
Front Neurosci. 2020 May 20;14:475. doi: 10.3389/fnins.2020.00475. eCollection 2020.
The increasing incidence of neurodegenerative diseases such as Alzheimer's or Parkinson's disease represents a significant burden for patients and national health systems. The conditions are primarily caused by the death of neurons and other neural cell types. One important aim of current stem cell research is to find a way to replace the lost cells. In this perspective, neural stem cells (NSCs) have been considered as a promising tool in the field of regenerative medicine. The behavior of NSCs is modulated by environmental influences, for example hormones, growth factors, cytokines, and extracellular matrix molecules or biomechanics. These factors can be studied by using well-defined hydrogels, which are polymeric networks of synthetic or natural origin with the ability to swell in water. These gels can be modified with a variety of molecules and optimized with regard to their mechanical properties to mimic the natural extracellular environment. In particular modifications applying distinct units such as functional domains and peptides can modulate the development of NSCs with regard to proliferation, differentiation and migration. One well-known peptide sequence that affects the behavior of NSCs is the integrin recognition sequence RGD that has originally been derived from fibronectin. In the present review we provide an overview concerning the applications of modified hydrogels with an emphasis on synthetic hydrogels based on poly(acrylamides), as modified with either cationic moieties or the peptide sequence RGD. This knowledge might be used in tissue engineering and regenerative medicine for the therapy of spinal cord injuries, neurodegenerative diseases and traumata.
诸如阿尔茨海默病或帕金森病等神经退行性疾病发病率的不断上升,给患者和国家卫生系统带来了沉重负担。这些病症主要是由神经元和其他神经细胞类型的死亡引起的。当前干细胞研究的一个重要目标是找到一种方法来替代丢失的细胞。从这个角度来看,神经干细胞(NSCs)被认为是再生医学领域一种有前景的工具。神经干细胞的行为受到环境影响的调节,例如激素、生长因子、细胞因子、细胞外基质分子或生物力学。这些因素可以通过使用定义明确的水凝胶来研究,水凝胶是具有在水中溶胀能力的合成或天然来源的聚合物网络。这些凝胶可以用各种分子进行修饰,并在其机械性能方面进行优化,以模拟天然细胞外环境。特别是应用不同单元(如功能域和肽)的修饰可以在增殖、分化和迁移方面调节神经干细胞的发育。一种影响神经干细胞行为的著名肽序列是整合素识别序列RGD,它最初源自纤连蛋白。在本综述中,我们概述了修饰水凝胶的应用,重点是基于聚(丙烯酰胺)的合成水凝胶,其用阳离子部分或肽序列RGD进行了修饰。这些知识可能用于组织工程和再生医学中治疗脊髓损伤、神经退行性疾病和创伤。