Department of Bioengineering, University of Pittsburgh, USA.
Department of Developmental Biology, University of Pittsburgh, USA.
Biomaterials. 2018 Jul;170:137-146. doi: 10.1016/j.biomaterials.2018.04.009. Epub 2018 Apr 6.
Mammalian central nervous system (CNS) has limited capacity for regeneration. CNS injuries cause life-long debilitation and lead to $50 billion in healthcare costs in U.S. alone each year. Despite numerous efforts in the last few decades, CNS-related injuries remain as detrimental as they were 50 years ago. Some functional recovery can occur, but most regeneration are limited by an extracellular matrix (ECM) that actively inhibits axonal repair and promotes glial scarring. In most tissues, the ECM is an architectural foundation that plays an active role in supporting cellular development and regenerative response after injury. In mammalian CNS, however, this is not the case - its composition is not conducive for regeneration, with various molecules restricting plasticity and neuronal growth. In fact, the CNS ECM alters its composition dramatically following injury to restrict regeneration and to prioritize containment of injury as well as preservation of intact neural circuitry. This leads us to hypothesize that the inhibitory extracellular environment needs be modified or supplemented to be more regeneration-permissive for significant CNS regeneration. Mammalian nervous tissue cannot provide such ECM, and synthesizing it in a laboratory is beyond current technology. Evolutionarily lower species possess remarkably regenerative neural tissue. For example, small fresh-water dwelling zebrafish (Danio rerio) can regenerate severed spinal cord, re-gaining full motor function in a week. We believe their ECM contributes to its regenerative capability and that it can be harnessed to induce more regeneration in mammalian CNS. This study shows that ECM derived from zebrafish brains promotes more neuronal survival and axonal network formation than the widely studied and available ECM derived from mammalian tissues such as porcine brains, porcine urinary bladder, and rat brains. We believe its regenerative potential, combined with its affordability, easy handling, and fast reproduction, will make zebrafish an excellent candidate as a novel ECM source.
哺乳动物中枢神经系统（CNS）的再生能力有限。CNS 损伤会导致终身残疾，仅在美国每年就造成 500 亿美元的医疗保健费用。尽管在过去几十年中做出了众多努力，但 CNS 相关损伤的危害性与 50 年前一样大。一些功能可以恢复，但大多数再生都受到细胞外基质（ECM）的限制，该基质积极抑制轴突修复并促进神经胶质瘢痕形成。在大多数组织中，ECM 是一种建筑基础，在支持细胞发育和受伤后再生反应方面发挥着积极作用。然而，在哺乳动物的 CNS 中，情况并非如此——其组成不利于再生，各种分子限制了可塑性和神经元生长。事实上，CNS ECM 在受伤后会剧烈改变其组成，以限制再生并优先控制损伤以及保持完整的神经回路。这使我们假设需要修饰或补充抑制性细胞外环境，使其更有利于 CNS 的显著再生。哺乳动物的神经组织无法提供这种 ECM，而在实验室中合成它则超出了当前的技术水平。进化程度较低的物种具有惊人的再生神经组织。例如，小型淡水斑马鱼（Danio rerio）可以再生切断的脊髓，在一周内恢复完全的运动功能。我们认为它们的 ECM 有助于其再生能力，并且可以利用它来诱导哺乳动物 CNS 中的更多再生。这项研究表明，来自斑马鱼大脑的 ECM 比广泛研究和可用的来自哺乳动物组织的 ECM（如猪脑、猪膀胱和鼠脑）更能促进神经元的存活和轴突网络的形成。我们相信其再生潜力，再加上其价格低廉、易于处理和快速繁殖，将使斑马鱼成为一种极好的新型 ECM 来源。
