Purvis Erin M, O'Donnell John C, Chen H Isaac, Cullen D Kacy
Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.
Front Neurol. 2020 Apr 28;11:344. doi: 10.3389/fneur.2020.00344. eCollection 2020.
Neurogenesis in the postnatal mammalian brain is known to occur in the dentate gyrus of the hippocampus and the subventricular zone. These neurogenic niches serve as endogenous sources of neural precursor cells that could potentially replace neurons that have been lost or damaged throughout the brain. As an example, manipulation of the subventricular zone to augment neurogenesis has become a popular strategy for attempting to replace neurons that have been lost due to acute brain injury or neurodegenerative disease. In this review article, we describe current experimental strategies to enhance the regenerative potential of endogenous neural precursor cell sources by enhancing cell proliferation in neurogenic regions and/or redirecting migration, including pharmacological, biomaterial, and tissue engineering strategies. In particular, we discuss a novel replacement strategy based on exogenously biofabricated "living scaffolds" that could enhance and redirect endogenous neuroblast migration from the subventricular zone to specified regions throughout the brain. This approach utilizes the first implantable, biomimetic tissue-engineered rostral migratory stream, thereby leveraging the brain's natural mechanism for sustained neuronal replacement by replicating the structure and function of the native rostral migratory stream. Across all these strategies, we discuss several challenges that need to be overcome to successfully harness endogenous neural precursor cells to promote nervous system repair and functional restoration. With further development, the diverse and innovative tissue engineering and biomaterial strategies explored in this review have the potential to facilitate functional neuronal replacement to mitigate neurological and psychiatric symptoms caused by injury, developmental disorders, or neurodegenerative disease.
已知产后哺乳动物大脑中的神经发生发生在海马体的齿状回和脑室下区。这些神经发生微环境作为神经前体细胞的内源性来源，有可能替代整个大脑中丢失或受损的神经元。例如，操纵脑室下区以增强神经发生已成为一种流行的策略，试图替代因急性脑损伤或神经退行性疾病而丢失的神经元。在这篇综述文章中，我们描述了当前的实验策略，即通过增强神经发生区域的细胞增殖和/或重新引导迁移来提高内源性神经前体细胞来源的再生潜力，包括药理学、生物材料和组织工程策略。特别是，我们讨论了一种基于外源性生物制造的“活支架”的新型替代策略，该策略可以增强并将内源性神经母细胞从脑室下区迁移重新引导至大脑的特定区域。这种方法利用了第一个可植入的、仿生组织工程化的嘴侧迁移流，从而通过复制天然嘴侧迁移流的结构和功能来利用大脑持续神经元替代的自然机制。在所有这些策略中，我们讨论了成功利用内源性神经前体细胞促进神经系统修复和功能恢复需要克服的几个挑战。随着进一步发展，本综述中探索的多样且创新的组织工程和生物材料策略有可能促进功能性神经元替代，以减轻由损伤、发育障碍或神经退行性疾病引起的神经和精神症状。
