Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering
Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering
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DOI：
10.1016/j.biomaterials.2012.11.043
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发表时间：
2013-03-01
期刊：
影响因子：
14
通讯作者：
Wang, Tzu-Wei
中科院分区：
文献类型：
--
作者：
Cheng, Tzu-Yun;Chen, Ming-Hong;Wang, Tzu-Wei
由于神经组织再生能力差，脑损伤几乎无法修复。如今，新的治疗策略已集中在干细胞疗法和提供适当的三维（3D）基质来修复受损的脑组织。在本研究中，我们将层粘连蛋白衍生的 IKVAV 基序特异性连接在 C 端，以丰富自组装肽 RADA(16) 作为功能性肽支架。我们的目的是提供一种具有封装神经干细胞的功能性自组装肽 3D 水凝胶，以增强受损大脑的重建。理化性质表明，RADA(16)-IKVAV可以自组装成具有双层β-折叠结构的纳米纤维形态，并成为具有与脑组织相似的机械刚度的凝胶化水凝胶。体外结果表明，扩展的 IKVAV 序列可以作为信号或引导线索，指导封装的神经干细胞（NSC）粘附，然后进行神经元分化。在大鼠脑部手术模型中进行动物研究，以证明大脑新皮质/新皮层损失的损伤。结果表明，注射的肽溶液立即在原位形成 3D 水凝胶，填充空腔并桥接间隙。组织学分析表明，RADA16-IKVAV 自组装肽水凝胶不仅提高了封装的 NSC 的存活率，而且还减少了胶质星形胶质细胞的形成。具有 IKVAV 扩展基序的肽水凝胶还显示出封装的 NSC 对神经元分化的支持以及移植后 6 周后脑组织再生的改善。 (C) 2012 Elsevier Ltd. 保留所有权利。
Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer beta-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA16-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. (C) 2012 Elsevier Ltd. All rights reserved.