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自体贴壁骨髓细胞鞘内移植可诱导犬脊髓损伤模型的神经功能恢复。

Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

作者信息

Gabr Hala, El-Kheir Wael Abo, Farghali Haithem A M A, Ismail Zeinab M K, Zickri Maha B, El Maadawi Zeinab M, Kishk Nirmeen A, Sabaawy Hatem E

机构信息

Department of Hematology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Cell Transplant. 2015;24(9):1813-27. doi: 10.3727/096368914X683025. Epub 2014 Jul 15.

Abstract

Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

摘要

脊髓损伤(SCI)会导致存活轴突的脱髓鞘、少突胶质细胞的丧失以及运动和感觉功能的损害。我们通过使用自体骨髓细胞进行移植,开发了一种针对SCI的细胞治疗临床策略,以增强髓鞘再生并促进神经修复。在一个临床前的大型哺乳动物SCI模型中,对实验犬进行脊髓夹伤挫伤。损伤两周后,将绿色荧光蛋白(GFP)标记的自体轻度处理的贴壁骨髓细胞(ABMCs)鞘内注射,以研究自体ABMC治疗的安全性和有效性。使用功能性神经评分来确定ABMC移植对SCI犬的影响,并通过组织病理学和免疫组织化学研究以及对对照和移植脊髓切片的电子显微镜分析来确定ABMCs在受损脊髓中的整合情况。我们的数据表明,在亚急性SCI阶段移植后长达16周,在受损脊髓中存在GFP标记的细胞。GFP标记的细胞归巢到损伤部位,并在白质束和存活轴突周围被检测到。犬SCI模型中的ABMC治疗增强了髓鞘再生并促进了神经再生,从而改善了神经功能。因此,自体ABMC治疗似乎是一种安全且有前景的脊髓损伤治疗方法。

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