间充质干细胞片促进亚急性脊髓损伤模型中的功能恢复并减轻神经性疼痛
Mesenchymal Stem Cell Sheet Promotes Functional Recovery and Palliates Neuropathic Pain in a Subacute Spinal Cord Injury Model.
作者信息
Yamazaki Kazuyoshi, Kawabori Masahito, Seki Toshitaka, Takamiya Soichiro, Konno Kotaro, Watanabe Masahiko, Houkin Kiyohiro, Fujimura Miki
机构信息
Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Japan.
Department of Anatomy and Embryology, Graduate School of Medicine, Hokkaido University, Japan.
出版信息
Stem Cells Int. 2021 Jul 9;2021:9964877. doi: 10.1155/2021/9964877. eCollection 2021.
Stem cell therapy has been shown to reverse the sequelae of spinal cord injury (SCI). Although the ideal treatment route remains unknown, providing a large number of stem cells to the injured site using less invasive techniques is critical to achieving maximal recovery. This study was conducted to determine whether administration of bone marrow stem cell (BMSC) sheet made on its own without a scaffold is superior to intramedullary cell transplantation in a rat subacute SCI model. Adult female Sprague-Dawley rats were subjected to SCI by 30 g clip compression at the level of Th6 and Th7 and were administered BMSC cell sheet (7 × 10 cells, subdural), cell suspension (7 × 10 cells, intramedullary), or control seven days after the injury. Motor and sensory assessments, as well as histological evaluation, were performed to determine the efficacy of the different cell transplantation procedures. While both the cell sheet and cell intramedullary injection groups showed significant motor recovery compared to the control group, the cell sheet group showed better results. Furthermore, the cell sheet group displayed a significant sensory recovery compared to the other groups. A histological evaluation revealed that the cell sheet group showed smaller injury lesion volume, less inflammation, and gliosis compared to other groups. Sensory-related fibers of -opioid receptors (MOR, interneuron) and hydroxytryptamine transporters (HTT, descending pain inhibitory pathway), located around the dorsal horn of the spinal cord at the caudal side of the SCI, were preserved only in the cell sheet group. Stem cells could also be found inside the peri-injured spinal cord in the cell sheet group. BMSC cell sheets were able to promote functional recovery and palliate neuropathic pain more effectively than intramedullary injections, thus serving as a good treatment option for SCI.
干细胞疗法已被证明可逆转脊髓损伤(SCI)的后遗症。尽管理想的治疗途径尚不清楚,但使用侵入性较小的技术将大量干细胞输送到损伤部位对于实现最大程度的恢复至关重要。本研究旨在确定在大鼠亚急性SCI模型中,无支架自制的骨髓干细胞(BMSC)片给药是否优于髓内细胞移植。成年雌性Sprague-Dawley大鼠在T6和T7水平通过30 g夹压造成SCI,并在损伤后7天给予BMSC细胞片(7×10个细胞,硬膜下)、细胞悬液(7×10个细胞,髓内)或对照组。进行运动和感觉评估以及组织学评估,以确定不同细胞移植程序的疗效。与对照组相比,细胞片组和细胞髓内注射组均显示出显著的运动恢复,但细胞片组效果更好。此外,与其他组相比,细胞片组显示出显著的感觉恢复。组织学评估显示,与其他组相比,细胞片组的损伤病变体积更小、炎症和胶质增生更少。位于SCI尾侧脊髓背角周围的阿片类受体(MOR,中间神经元)和5-羟色胺转运体(HTT,下行疼痛抑制通路)的感觉相关纤维仅在细胞片组中得以保留。在细胞片组中,还可在损伤周围的脊髓内发现干细胞。BMSC细胞片比髓内注射更能有效地促进功能恢复和缓解神经性疼痛,因此是SCI的一种良好治疗选择。