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经修饰的去细胞神经递质平滑肌细胞可改善完全性脊髓横断大鼠的功能恢复。

Modified acellular nerve-delivering PMSCs improve functional recovery in rats after complete spinal cord transection.

机构信息

Institute of Human Anatomy and Histology and Embryology, Otology & Neuroscience Center, Binzhou Medical University, 346 Guanhai Road, Laishan District, Shandong Province 264003, China.

出版信息

Biomater Sci. 2017 Nov 21;5(12):2480-2492. doi: 10.1039/c7bm00485k.

DOI:10.1039/c7bm00485k
PMID:29106428
Abstract

Due to the poor regeneration capacity of neurons and the inhibitory microenvironment, spontaneous regeneration in spinal cord injury (SCI) remains challenging. Tissue engineering is considered a promising approach for enhancing the regeneration of SCI by reconstructing the inherent structure and improving the microenvironment. In this study, the possibility of engineering a nerve complex, which is constructed by acellular nerve delivering placenta mesenchymal stem cells (PMSCs), was assessed for the recovery of a transected spinal cord. Modified acellular nerve grafts were developed, and PMSCs labeled with green fluorescent protein (GFP) were seeded on the graft to construct the engineered nerve complex. Then, the engineered nerve complex was implanted into a 2 mm-length transected gap of the spinal cord. Four weeks after the transplantation, numerous surviving PMSCs were observed in the lesion cavity by immunofluorescence staining. Moreover, co-localization between GFP and neurofilament-200 (NF200) and Neuronal Class III β-Tubulin (Tuj1) was observed at the bridge interface. The PMSCs-graft group exhibited significant function improvement as evaluated by the Basso, Beattie and Bresnahan (BBB) locomotion score and footprint analysis. Eight weeks after surgery, the evoked response was restored in the PMSCs-graft group and numerous thick myelin sheathes were observed compared to that in the control groups. Collectively, our findings suggest that the nerve complex prepared by acellular nerve delivering PMSCs enhanced the structure and function regeneration of the spinal cord after SCI.

摘要

由于神经元的再生能力差和抑制性微环境,脊髓损伤 (SCI) 的自发再生仍然具有挑战性。组织工程被认为是一种有前途的方法,可以通过重建固有结构和改善微环境来增强 SCI 的再生。在这项研究中,通过将无细胞神经递送来的胎盘间充质干细胞 (PMSC) 构建成神经复合体,评估了其用于修复脊髓横断的可能性。制备了改良的无细胞神经移植物,并将绿色荧光蛋白 (GFP) 标记的 PMSC 接种在移植物上构建工程神经复合体。然后,将工程神经复合体植入脊髓 2mm 长的横断间隙中。移植后 4 周,通过免疫荧光染色在损伤腔中观察到大量存活的 PMSC。此外,在桥接界面处观察到 GFP 与神经丝-200 (NF200) 和神经元 III 类 β-微管蛋白 (Tuj1) 的共定位。Basso、Beattie 和 Bresnahan (BBB) 运动评分和足迹分析评估显示,PMSC-移植物组的功能明显改善。手术后 8 周,在 PMSC-移植物组中恢复了诱发电位,与对照组相比,观察到大量厚的髓鞘。总之,我们的研究结果表明,由无细胞神经递送来的 PMSC 制备的神经复合体增强了 SCI 后脊髓的结构和功能再生。

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