Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration
Long-Term Survival and Integration of Transplanted Engineered Nervous Tissue Constructs Promotes Peripheral Nerve Regeneration
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DOI：
10.1089/ten.tea.2008.0294
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发表时间：
2009-07-01
影响因子：
4.1
通讯作者：
Smith, Douglas H.
中科院分区：
文献类型：
--
作者：
Huang, Jason H.;Cullen, D. Kacy;Smith, Douglas H.
虽然周围神经损伤是创伤或手术的常见后果，但修复手段不足。特别地，迫切需要改进的方法来促进跨越主要神经损伤的轴突再生。在这里，我们设计了可移植的活神经组织结构，以提供一个标记的途径来指导宿主轴突再生。这些结构包括拉伸生长，纵向对齐的活轴突束插入聚（乙醇酸）管。将构建体（同种异体）移植到大鼠坐骨神经切除段，并在移植后6周和16周进行组织学分析，以确定移植物存活、整合和宿主再生。在这两个时间点，移植的构建体被发现保持其移植前的几何形状，在轴突束跨越的构建体的末端具有存活的移植神经元胞体簇。在整个移植区域，有宿主和移植物轴突的交织丛，表明移植的轴突介导宿主轴突再生穿过损伤。移植后16周，在整个移植区域观察到广泛的轴突髓鞘形成。此外，移植神经元的轴突延伸到移植区域的边缘之外，穿透宿主神经。值得注意的是，这种同种异体构建体的存活和整合发生在没有免疫抑制治疗的情况下。这些研究结果表明，活的组织工程轴突结构的承诺，以桥梁主要的神经病变和促进宿主再生，可能通过提供轴突介导的轴突生长和指导。
Although peripheral nerve injury is a common consequence of trauma or surgery, there are insufficient means for repair. In particular, there is a critical need for improved methods to facilitate regeneration of axons across major nerve lesions. Here, we engineered transplantable living nervous tissue constructs to provide a labeled pathway to guide host axonal regeneration. These constructs consisted of stretch-grown, longitudinally aligned living axonal tracts inserted into poly(glycolic acid) tubes. The constructs (allogenic) were transplanted to bridge an excised segment of sciatic nerve in the rat, and histological analyses were performed at 6 and 16 weeks posttransplantation to determine graft survival, integration, and host regeneration. At both time points, the transplanted constructs were found to have maintained their pretransplant geometry, with surviving clusters of graft neuronal somata at the extremities of the constructs spanned by tracts of axons. Throughout the transplanted region, there was an intertwining plexus of host and graft axons, suggesting that the transplanted axons mediated host axonal regeneration across the lesion. By 16 weeks posttransplant, extensive myelination of axons was observed throughout the transplant region. Further, graft neurons had extended axons beyond the margins of the transplanted region, penetrating into the host nerve. Notably, this survival and integration of the allogenic constructs occurred in the absence of immunosuppression therapy. These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance.