Iwata Akira, Browne Kevin D, Pfister Bryan J, Gruner John A, Smith Douglas H
Department of Neurosurgery, Center for Brain Injury Repair, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tissue Eng. 2006 Jan;12(1):101-10. doi: 10.1089/ten.2006.12.101.
While most approaches to repair spinal cord injury (SCI) rely on promoting axon outgrowth, the extensive distance that axons would have to grow to bridge SCI lesions remains an enormous challenge. In this study, we used a new tissue-engineering technique to create long nervous tissue constructs spanned by living axon tracts to repair long SCI lesions. Exploiting the newfound process of extreme axon stretch growth, integrated axon tracts from dorsal root ganglia (DRG) neurons were mechanically elongated in vitro to 10 mm over 7 days and encased in a collagen hydrogel to form a nervous tissue construct. In addition, a modified lateral hemisection SCI model in the rat was developed to create a 1 cm long cavity in the spinal cord. Ten days following SCI, constructs were transplanted into the lesion and the animals were euthanized 4 weeks post-transplantation for histological analyses. Through cell tracking methods and immunohistochemistry, the transplanted elongated cultures were consistently found to survive 4 weeks in the injured spinal cord. In addition, DRG axons were observed extending out of the transplanted construct into the host spinal cord tissue. These results demonstrate the promise of nervous tissue constructs consisting of stretch-grown axons to bridge even extensive spinal cord lesions.
虽然大多数修复脊髓损伤（SCI）的方法都依赖于促进轴突生长，但轴突要生长很长距离才能跨越SCI损伤部位，这仍然是一个巨大的挑战。在本研究中，我们使用一种新的组织工程技术来创建由活轴突束跨越的长神经组织构建体，以修复长距离的SCI损伤。利用新发现的轴突极端拉伸生长过程，将背根神经节（DRG）神经元的整合轴突束在体外机械拉长至10毫米，历时7天，然后包裹在胶原水凝胶中形成神经组织构建体。此外，还建立了一种改良的大鼠侧半横断SCI模型，在脊髓中创建一个1厘米长的空洞。SCI术后10天，将构建体移植到损伤部位，移植后4周对动物实施安乐死以进行组织学分析。通过细胞追踪方法和免疫组织化学，持续发现移植的拉长培养物在受损脊髓中存活了4周。此外，观察到DRG轴突从移植构建体延伸到宿主脊髓组织中。这些结果表明，由拉伸生长的轴突组成的神经组织构建体有望跨越甚至广泛的脊髓损伤。
