Department of Clinical Neurosciences and National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Cell Tissue Res. 2022 Mar;387(3):399-414. doi: 10.1007/s00441-021-03554-0. Epub 2021 Nov 25.
Glial scars are a common pathological occurrence in a variety of central nervous system (CNS) diseases and injuries. They are caused after severe damage and consist of reactive glia that form a barrier around the damaged tissue that leads to a non-permissive microenvironment which prevents proper endogenous regeneration. While there are a number of therapies that are able to address some components of disease, there are none that provide regenerative properties. Within the past decade, neural stem cells (NSCs) have been heavily studied due to their potent anti-inflammatory and reparative capabilities in disease and injury. Exogenously applied NSCs have been found to aid in glial scar healing by reducing inflammation and providing cell replacement. However, endogenous NSCs have also been found to contribute to the reactive environment by different means. Further understanding how NSCs can be leveraged to aid in the resolution of the glial scar is imperative in the use of these cells as regenerative therapies. To do so, humanised 3D model systems have been developed to study the development and maintenance of the glial scar. Herein, we explore the current work on endogenous and exogenous NSCs in the glial scar as well as the novel 3D stem cell-based technologies being used to model this pathology in a dish.
胶质瘢痕是多种中枢神经系统（CNS）疾病和损伤中的一种常见病理现象。它们是在严重损伤后形成的，由反应性胶质组成，在损伤组织周围形成一个屏障，导致非许可性的微环境，从而阻止适当的内源性再生。虽然有许多治疗方法能够解决疾病的某些方面，但没有一种方法能够提供再生特性。在过去的十年中，神经干细胞（NSC）因其在疾病和损伤中的强大抗炎和修复能力而受到广泛研究。研究发现，外源性 NSCs 通过减少炎症和提供细胞替代来帮助胶质瘢痕愈合。然而，内源性 NSCs 也通过不同的方式对反应性环境做出贡献。进一步了解如何利用 NSCs 来帮助解决胶质瘢痕问题，对于将这些细胞作为再生疗法的应用至关重要。为此，已经开发了人源化 3D 模型系统来研究胶质瘢痕的发育和维持。本文探讨了内源性和外源性 NSCs 在胶质瘢痕中的作用，以及新型基于干细胞的 3D 技术在体外模拟该病理过程中的应用。
