Department of Histology and Embryology, Medical College, Nantong University, Nantong, Jiangsu, China.
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, China.
J Tissue Eng Regen Med. 2020 Mar;14(3):397-411. doi: 10.1002/term.2996. Epub 2020 Jan 29.
As a result of its complex histological structure, regeneration patterns of grey and white matter are quite different in the spinal cord. Therefore, tissue engineering scaffolds for repairing spinal cord injury must be able to adapt to varying neural regeneration patterns. The aim of the present study was to improve a previously reported spinal cord-mimicking partition-type scaffold by adding microchannels on a single tubular wall along its longitudinal axis, thus integrating the two architectures of a single H-shaped central tube and many microchannels. Next, the integrated scaffold was loaded with bone marrow stromal cells (BMSCs) and transplanted to bridge the 5-mm defect of a complete transverse lesion in the thoracic spinal cord of rats. Subsequently, effects on nerve regeneration, locomotion function recovery, and early neuroprotection were observed. After 1 year of repair, the integrated scaffold could guide the regeneration of axons appearing in the debris of degraded microchannels, especially serotonin receptor 1A receptor-positive axonal tracts, which were relatively orderly arranged. Moreover, a network of nerve fibres was present, and a few BMSCs expressed neuronal markers in tubular lumens. Functionally, electrophysiological and locomotor functions of rats were partially recovered. In addition, we found that BMSCs could protect neurons and oligodendrocytes from apoptosis during the early stage of implantation. Taken together, our results demonstrate the potential of this novel integrated scaffold loaded with BMSCs to promote spinal cord regeneration through mechanical guidance and neuroprotective mechanisms.
由于其复杂的组织学结构,脊髓内灰质和白质的再生模式有很大的不同。因此,用于修复脊髓损伤的组织工程支架必须能够适应不同的神经再生模式。本研究的目的是通过在单一管状壁上沿其纵轴添加微通道来改进先前报道的脊髓模拟分区式支架,从而整合单个 H 形中央管和许多微通道的两种结构。接下来,将整合的支架加载骨髓基质细胞(BMSCs)并移植到大鼠胸段完全横断损伤的 5mm 缺损处。随后,观察对神经再生、运动功能恢复和早期神经保护的影响。修复 1 年后,整合的支架可以引导在降解的微通道碎片中出现的轴突的再生,特别是血清素受体 1A 受体阳性的轴突束,它们排列相对有序。此外,存在神经纤维网络,并且在管腔中有一些 BMSCs 表达神经元标记物。在功能上,大鼠的电生理学和运动功能得到了部分恢复。此外,我们发现 BMSCs 可以在植入的早期保护神经元和少突胶质细胞免受凋亡。综上所述,我们的研究结果表明,这种新型的 BMSCs 负载的整合支架具有通过机械引导和神经保护机制促进脊髓再生的潜力。