Raymond Purves Bone and Joint Research Laboratory, Kolling Institute, Northern Sydney Local Health District, St. Leonards, NSW 2065, Australia.
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Int J Mol Sci. 2022 May 5;23(9):5148. doi: 10.3390/ijms23095148.
The aim of this study was to illustrate recent developments in neural repair utilizing hyaluronan as a carrier of olfactory bulb stem cells and in new bioscaffolds to promote neural repair. Hyaluronan interacts with brain hyalectan proteoglycans in protective structures around neurons in perineuronal nets, which also have roles in the synaptic plasticity and development of neuronal cognitive properties. Specialist stem cell niches termed fractones located in the sub-ventricular and sub-granular regions of the dentate gyrus of the hippocampus migrate to the olfactory bulb, which acts as a reserve of neuroprogenitor cells in the adult brain. The extracellular matrix associated with the fractone stem cell niche contains hyaluronan, perlecan and laminin α5, which regulate the quiescent recycling of stem cells and also provide a means of escaping to undergo the proliferation and differentiation to a pluripotent migratory progenitor cell type that can participate in repair processes in neural tissues. Significant improvement in the repair of spinal cord injury and brain trauma has been reported using this approach. FGF-2 sequestered by perlecan in the neuroprogenitor niche environment aids in these processes. Therapeutic procedures have been developed using olfactory ensheathing stem cells and hyaluronan as a carrier to promote neural repair processes. Now that recombinant perlecan domain I and domain V are available, strategies may also be expected in the near future using these to further promote neural repair strategies.
本研究旨在阐述利用透明质酸作为嗅球干细胞载体以及新型生物支架促进神经修复的最新进展。透明质酸与脑透明质酸糖蛋白相互作用,形成神经元周围保护性结构中的神经周细胞网络,这些结构在突触可塑性和神经元认知特性的发育中也具有重要作用。位于海马齿状回室下区和颗粒下层的专门干细胞小生境称为 fractones,它们迁移到嗅球,嗅球在成人脑中充当神经祖细胞的储备库。与 fractone 干细胞小生境相关的细胞外基质含有透明质酸、perlecan 和层粘连蛋白 α5,它们调节干细胞的静止循环,还提供了一种逃避增殖和分化为多能迁移祖细胞类型的方式,这种细胞类型可以参与神经组织的修复过程。利用这种方法,已经报道了在脊髓损伤和脑创伤修复方面的显著改善。perlecan 结合的 FGF-2 在神经祖细胞小生境环境中有助于这些过程。已经开发出了使用嗅鞘细胞和透明质酸作为载体来促进神经修复过程的治疗方法。现在已经可以获得重组的 perlecan 结构域 I 和结构域 V,预计在不久的将来也可以使用这些结构域来进一步促进神经修复策略。