Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), Neuroscience Section, University of Milan, Milan, Italy.
Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122, Milan, Italy.
Mol Neurobiol. 2019 May;56(5):3356-3367. doi: 10.1007/s12035-018-1305-4. Epub 2018 Aug 17.
Despite the extensive research effort that has been made in the field, motor neuron diseases, namely, amyotrophic lateral sclerosis and spinal muscular atrophies, still represent an overwhelming cause of morbidity and mortality worldwide. Exogenous neural stem cell-based transplantation approaches have been investigated as multifaceted strategies to both protect and repair upper and lower motor neurons from degeneration and inflammation. Transplanted neural stem cells (NSCs) exert their beneficial effects not only through the replacement of damaged cells but also via bystander immunomodulatory and neurotrophic actions. Notwithstanding these promising findings, the clinical translatability of such techniques is jeopardized by the limited engraftment success and survival of transplanted cells within the hostile disease microenvironment. To overcome this obstacle, different methods to enhance graft survival, stability, and therapeutic potential have been developed, including environmental stress preconditioning, biopolymers scaffolds, and genetic engineering. In this review, we discuss current engineering techniques aimed at the exploitation of the migratory, proliferative, and secretive capacity of NSCs and their relevance for the therapeutic arsenal against motor neuron disorders and other neurological disorders.
尽管在该领域已经进行了广泛的研究，但运动神经元疾病，即肌萎缩侧索硬化症和脊髓性肌萎缩症，仍然是全世界发病率和死亡率的主要原因。外源性神经干细胞移植方法已被作为一种多方面的策略进行研究，以保护和修复上下运动神经元免受变性和炎症的侵害。移植的神经干细胞（NSCs）不仅通过替代受损细胞，而且通过旁观者免疫调节和神经营养作用发挥其有益作用。尽管有这些有希望的发现，但这些技术的临床转化受到移植细胞在恶劣的疾病微环境中的有限植入成功率和存活率的威胁。为了克服这一障碍，已经开发了不同的方法来增强移植物的存活、稳定性和治疗潜力，包括环境应激预处理、生物聚合物支架和基因工程。在这篇综述中，我们讨论了目前旨在利用 NSCs 的迁移、增殖和分泌能力的工程技术，以及它们对治疗运动神经元疾病和其他神经退行性疾病的治疗武器的相关性。
