BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration
BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration
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DOI：
10.1088/1741-2560/13/6/066011
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发表时间：
2016-12-01
影响因子：
4
通讯作者：
Tuszynski, Mark
中科院分区：
文献类型：
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作者：
Gao, Mingyong;Lu, Paul;Tuszynski, Mark
目标。我们将多通道模板琼脂糖支架植入和生长因子基因转移相结合，以检测这种联合治疗是否可以通过长时间的坐骨神经间隙促进周围轴突的再生。接近。15 mm长的支架被模板化成高度组织的、严格的线性通道，模拟自然神经的线性组织成相关功能的神经束。将分泌生长因子脑源性神经营养因子的同基因骨髓基质细胞填充支架，将表达脑源性神经营养因子的慢病毒载体注射到支架植入部位远端的坐骨神经节段。主要结果。损伤后12周，支架支持宿主轴突在15 mm的损伤间隙内高度线性再生。将分泌BDNF的细胞整合到支架中显著增加了轴突的再生，另外将表达BDNF的病毒载体注射到横断神经的远端显著促进了损伤以外的轴突再生。意义重大。多通道生物工程支架和远端生长因子输送的组合治疗显著改善了周围神经修复，可与自体移植的黄金标准相媲美。
Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.