Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery
Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery
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DOI：
10.1016/j.biomaterials.2023.122003
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发表时间：
2023-02-02
期刊：
影响因子：
14
通讯作者：
Sawamoto，Kazunobu
中科院分区：
文献类型：
--
作者：
Ohno，Yuya;Nakajima，Chikako;Sawamoto，Kazunobu
哺乳动物大脑在损伤后再生丢失的神经元和恢复功能的能力非常有限。使用生物材料促进源自内源性神经干细胞的年轻神经元（神经母细胞）的迁移是一种新的、有前途的方法，有助于大脑损伤后的恢复。然而，由于可用于引导神经母细胞迁移的支架细胞数量有限，将足够的神经母细胞输送到远处的损伤部位是一个重大挑战。为了解决这个问题，我们开发了一种两亲肽[(RADA)3-(RADG)] (mRADA)标记的N-钙粘蛋白胞外结构域(Ncad-mRADA)，它可以保留在mRADA水凝胶中并注射到深部脑组织中以促进神经母细胞迁移。迁移的神经母细胞直接接触纤维状的 Ncad-mRADA 水凝胶，并有效地迁移到纹状体（大脑深部区域）的损伤部位。此外，Ncad-mRADA应用于新生儿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 Ncad-mRADA 肽模拟了内源性支架细胞的功能和结构，并为再生治疗提供了一种新策略。
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)3-(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.