Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan; Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan.
Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan.
Biomaterials. 2023 Mar;294:122003. doi: 10.1016/j.biomaterials.2023.122003. Epub 2023 Jan 17.
The mammalian brain has very limited ability to regenerate lost neurons and recover function after injury. Promoting the migration of young neurons (neuroblasts) derived from endogenous neural stem cells using biomaterials is a new and promising approach to aid recovery of the brain after injury. However, the delivery of sufficient neuroblasts to distant injured sites is a major challenge because of the limited number of scaffold cells that are available to guide neuroblast migration. To address this issue, we have developed an amphiphilic peptide [(RADA)-(RADG)] (mRADA)-tagged N-cadherin extracellular domain (Ncad-mRADA), which can remain in mRADA hydrogels and be injected into deep brain tissue to facilitate neuroblast migration. Migrating neuroblasts directly contacted the fiber-like Ncad-mRADA hydrogel and efficiently migrated toward an injured site in the striatum, a deep brain area. Furthermore, application of Ncad-mRADA to neonatal cortical brain injury efficiently promoted neuronal regeneration and functional recovery. These results demonstrate that self-assembling Ncad-mRADA peptides mimic both the function and structure of endogenous scaffold cells and provide a novel strategy for regenerative therapy.
哺乳动物的大脑再生丢失的神经元和在损伤后恢复功能的能力非常有限。使用生物材料促进内源性神经干细胞产生的年轻神经元（神经母细胞）的迁移是一种新的、有前途的方法，可以帮助大脑在损伤后恢复。然而，由于可用的支架细胞数量有限，难以将足够数量的神经母细胞输送到远处的损伤部位，从而限制了它们的迁移。为了解决这个问题，我们开发了一种两亲性肽 [(RADA)-(RADG)]（mRADA）标记的 N 钙粘蛋白细胞外域（Ncad-mRADA），它可以保留在 mRADA 水凝胶中，并注入深部脑组织，以促进神经母细胞的迁移。迁移的神经母细胞直接与纤维状的 Ncad-mRADA 水凝胶接触，并有效地向纹状体（深部脑区）的损伤部位迁移。此外，将 Ncad-mRADA 应用于新生皮质脑损伤可有效促进神经元再生和功能恢复。这些结果表明，自组装的 Ncad-mRADA 肽模拟了内源性支架细胞的功能和结构，为再生治疗提供了一种新策略。
