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评估用于治疗创伤后脊髓空洞症及慢性脊髓损伤后运动功能恢复的间充质干细胞最佳植入数量

Evaluation of the Optimal Number of Implanted Mesenchymal Stem Cells for the Treatment of Post-Traumatic Syrinx and Recovery of Motor Activity after Chronic Spinal Cord Injury.

作者信息

Zhang C, Morozova A Yu, Abakumov M A, Mel'nikov P A, Gabashvili A N, Chekhonin V P

机构信息

Department of Medicinal Nanobiotechnology, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.

Department of Basic and Applied Neurobiology, V. P. Serbsky National Medical Research Center for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2023 Aug;175(4):557-568. doi: 10.1007/s10517-023-05904-0. Epub 2023 Sep 29.

Abstract

The present work aims at determining the most effective dose (number) of mesenchymal stem cells (MSC) for its transplantation in order to treat chronic spinal cord injury (SCI) in mature Sprague-Dawley rats (n=24). MSC were obtained from bone marrow of 4-6-month-old Sprague-Dawley rats. Four weeks after SCI, MSC suspension (4 μl) was injected to experimental animals into the injured area in doses of 4×10, 8×10, or 10. Using MRI, diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), immunohistochemistry, histological staining, and behavioral tests, we studied the effect of transplantation of MSC in different doses on the following parameters in rats with SCI: the size of lesion cavity and post-traumatic syrinx (PTS), glial scar formation, neuronal fibers remodeling, axonal regeneration and sprouting, vascularization, expression of neuronal factors, and motor functions. MSC administration improved motor function in rats after SCI due to stimulation of regeneration and sprouting of the axons, enhanced recovery of locomotor functions, reduction of PTS and the glial scar, and stimulation of vascularization and expression of the neurotrophic factors. The effects of MSC were dose-dependent; the most effective dose was 10 cells.

摘要

本研究旨在确定间充质干细胞(MSC)移植治疗成年Sprague-Dawley大鼠(n = 24)慢性脊髓损伤(SCI)的最有效剂量(数量)。MSC取自4至6月龄Sprague-Dawley大鼠的骨髓。脊髓损伤四周后,将MSC悬液(4 μl)以4×10、8×10或10的剂量注射到实验动物的损伤区域。通过磁共振成像(MRI)、扩散张量成像(DTI)、扩散张量纤维束成像(DTT)、免疫组织化学、组织学染色和行为测试,我们研究了不同剂量的MSC移植对SCI大鼠以下参数的影响:损伤腔和创伤后空洞(PTS)的大小、胶质瘢痕形成、神经纤维重塑、轴突再生和发芽、血管生成、神经因子表达以及运动功能。给予MSC可改善SCI大鼠的运动功能,这是由于刺激了轴突的再生和发芽、增强了运动功能的恢复、减少了PTS和胶质瘢痕,以及刺激了血管生成和神经营养因子的表达。MSC的作用呈剂量依赖性;最有效的剂量是10个细胞。

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