Gao Mingyong, Lu Paul, Lynam Dan, Bednark Bridget, Campana W Marie, Sakamoto Jeff, Tuszynski Mark
Departments of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
J Neural Eng. 2016 Dec;13(6):066011. doi: 10.1088/1741-2560/13/6/066011. Epub 2016 Oct 20.
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.
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.
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.
Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.
我们将多通道模板化琼脂糖支架植入与生长因子基因递送相结合，以研究这种联合治疗是否能促进坐骨神经长节段外周轴突再生。
将15毫米长的支架制成高度有序、严格呈线性排列的通道，模拟天然神经按相关功能束状排列的线性结构。支架填充分泌生长因子脑源性神经营养因子（BDNF）的同基因骨髓基质细胞（MSC），并将表达BDNF的慢病毒载体注射到支架植入部位远端的坐骨神经节段。
损伤12周后，支架支持宿主轴突跨越15毫米的损伤间隙进行高度线性再生。将分泌BDNF的细胞整合到支架中显著增加了轴突再生，并且向横断神经的远端节段额外注射表达BDNF的病毒载体显著增强了损伤部位以外的轴突再生。
多通道生物工程支架与远端生长因子递送的联合治疗显著改善了外周神经修复，可与自体移植的金标准相媲美。
