Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis
Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis
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DOI：
10.3109/14653249.2011.592521
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发表时间：
2011-10-01
期刊：
影响因子：
4.5
通讯作者：
Sykova, Eva
中科院分区：
文献类型：
--
作者：
Forostyak, Serhiy;Jendelova, Pavla;Sykova, Eva
背景目标。肌萎缩侧索硬化症（ALS）是一种以脑和脊髓运动神经元（MN）缺失为特征的进行性神经退行性疾病。采用骨髓间充质干细胞（MSC）椎管内和全身移植治疗过表达人超氧化物歧化酶1（SOD 1）的转基因大鼠，以减轻疾病进程，延长动物寿命。方法.在16周龄（疾病发作）时，大鼠在同一天接受两种表达绿色荧光蛋白的MSC（GFP（+）MSC）移植物，脊柱内（10（5）个细胞）和静脉内（2 × 10（6）个细胞）。用磷酸盐缓冲盐水（PBS）注射假处理的动物。测试运动活动、握力和体重，然后进行免疫组织化学分析。结果MSC联合移植到有症状的大鼠中对移植后4周开始的运动活动和握力有显着影响。给药组动物的寿命为190 +/- 3.33天，而对照组动物的寿命为179 +/- 3.6天。治疗组大鼠在胸部和腰部水平有大量的MN，这些MN的尺寸较大，在胸部水平凋亡MN的胞体中末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）染色的强度远低于假手术治疗的动物。移植的GFP（+）MSC在脊髓中存活至疾病的终末期，并从注射部位向吻侧和尾侧迁移。结论. MSC的椎管内和静脉内移植对ALS动物的寿命具有有益的和可能的协同作用。
Background aims. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of brain and spinal cord motor neurons (MN). The intraspinal and systemic grafting of mesenchymal stromal cells (MSC) was used to treat symptomatic transgenic rats overexpressing human superoxide dismutase 1 (SOD1) in order to alleviate the disease course and prolong the animals 'lifespan. Methods. At the age of 16 weeks (disease onset) the rats received two grafts of MSC expressing green fluorescent protein (GFP(+) MSC) on the same day, intraspinally (10(5) cells) and intravenously (2 x 10(6) cells). Sham-treated animals were injected with phosphate-buffered saline (PBS). Motor activity, grip strength and body weight were tested, followed by immunohistochemical analysis. Results. The combined grafting of MSC into symptomatic rats had a significant effect on motor activity and grip strength starting 4 weeks after transplantation. The lifespan of animals in the treated group was 190 +/- 3.33 days compared with 179 +/- 3.6 days in the control group of animals. Treated rats had a larger number of MN at the thoracic and lumbar levels; these MN were of larger size, and the intensity of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining in the somas of apoptotic MN at the thoracic level was much lower than in sham-treated animals. Transplanted GFP(+) MSC survived in the spinal cord until the end stage of the disease and migrated both rostrally and caudally from the injection site. Conclusions. Intraspinal and intravenous transplantation of MSC has a beneficial and possibly synergistic effect on the lifespan of ALS animals.