Lacalle-Aurioles María, Cassel de Camps Camille, Zorca Cornelia E, Beitel Lenore K, Durcan Thomas M
Early Drug Discovery Unit, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
Department of Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada.
Front Cell Neurosci. 2020 Nov 12;14:594304. doi: 10.3389/fncel.2020.594304. eCollection 2020.
Traumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults and has a profound impact on the socio-economic wellbeing of patients and their families. Initially, brain damage is caused by mechanical stress-induced axonal injury and vascular dysfunction, which can include hemorrhage, blood-brain barrier disruption, and ischemia. Subsequent neuronal degeneration, chronic inflammation, demyelination, oxidative stress, and the spread of excitotoxicity can further aggravate disease pathology. Thus, TBI treatment requires prompt intervention to protect against neuronal and vascular degeneration. Rapid advances in the field of stem cells (SCs) have revolutionized the prospect of repairing brain function following TBI. However, more than that, SCs can contribute substantially to our knowledge of this multifaced pathology. Research, based on human induced pluripotent SCs (hiPSCs) can help decode the molecular pathways of degeneration and recovery of neuronal and glial function, which makes these cells valuable tools for drug screening. Additionally, experimental approaches that include hiPSC-derived engineered tissues (brain organoids and bio-printed constructs) and biomaterials represent a step forward for the field of regenerative medicine since they provide a more suitable microenvironment that enhances cell survival and grafting success. In this review, we highlight the important role of hiPSCs in better understanding the molecular pathways of TBI-related pathology and in developing novel therapeutic approaches, building on where we are at present. We summarize some of the most relevant findings for regenerative therapies using biomaterials and outline key challenges for TBI treatments that remain to be addressed.
创伤性脑损伤（TBI）是儿童和青年致残和致死的主要原因，对患者及其家庭的社会经济福祉产生深远影响。最初，脑损伤是由机械应力诱导的轴突损伤和血管功能障碍引起的，这可能包括出血、血脑屏障破坏和缺血。随后的神经元变性、慢性炎症、脱髓鞘、氧化应激和兴奋性毒性的扩散会进一步加重疾病病理。因此，TBI治疗需要及时干预以防止神经元和血管变性。干细胞（SCs）领域的快速发展彻底改变了TBI后修复脑功能的前景。然而，更重要的是，SCs可以极大地增进我们对这种多方面病理的了解。基于人类诱导多能干细胞（hiPSCs）的研究有助于解码神经元和神经胶质功能退变和恢复的分子途径，这使这些细胞成为药物筛选的宝贵工具。此外，包括hiPSC衍生的工程组织（脑类器官和生物打印构建体）和生物材料的实验方法代表了再生医学领域向前迈进的一步，因为它们提供了更合适的微环境，可提高细胞存活率和移植成功率。在这篇综述中，我们重点介绍了hiPSCs在更好地理解TBI相关病理的分子途径以及开发新治疗方法方面的重要作用，基于我们目前的研究进展。我们总结了使用生物材料进行再生治疗的一些最相关的发现，并概述了TBI治疗仍有待解决的关键挑战。
