Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
Brain Res. 2011 Jul 21;1402:122-31. doi: 10.1016/j.brainres.2011.05.055. Epub 2011 May 30.
Cerebellar ataxias, which comprise a wide spectrum of progressive disorders, are incurable at present. It has been reported that human umbilical mesenchymal stem cell (HU-MSC) transplantation has a protective effect on neurodegenerative diseases. In this study, we investigated the effect of HU-MSCs on ataxic mice induced by cytosine beta-D-arabinofuranoside (Ara-C). The ataxic mouse received an intravenous injection of 2×10(6) HU-MSCs once a week for three consecutive weeks. Neurological function was scored weekly by rotarod test and open field test. The mouse cerebellar volume and weight were also measured. The apoptotic cells, pathological alternations and distribution of HU-MSCs were determined by TUNEL assay and immunohistochemistry staining respectively. Double immunostaining was carried out to investigate the dynamics of HU-MSCs in the host animals. Neurotrophic factors in cerebellar tissue and serum were measured by Q-PCR and ELISA. Our results showed that HU-MSCs implantation significantly improved the motor skills of ataxic mice 8 weeks after application. HU-MSCs also alleviated cerebellar atrophy and decreased the number of apoptotic cells in the therapeutic group. Implanted HU-MSCs stayed in cerebellum for at least three months with no obvious differentiation. HU-MSC treated mice had enhanced expression of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in cerebellum extraction and blood serum. Double immunostaining revealed that a few MAB1287 positive cells co-localized with IGF-1 or VEGF express cells. Our results suggest that HU-MSC treatment is capable of alleviating the motor impairments and cerebellar atrophy in the ataxic mouse model, probably via promoting particular neurotrophic factors.
小脑共济失调是一组广泛的进行性疾病，目前尚无治愈方法。有报道称，人脐带来源间充质干细胞（HU-MSC）移植对神经退行性疾病具有保护作用。在本研究中，我们研究了 HU-MSC 对阿糖胞苷（Ara-C）诱导的共济失调小鼠的作用。共济失调小鼠每周静脉注射 2×10(6)个 HU-MSC，连续 3 周。每周通过转棒试验和旷场试验对神经功能进行评分。还测量了小鼠小脑的体积和重量。通过 TUNEL 检测和免疫组织化学染色分别确定凋亡细胞、病理改变和 HU-MSC 的分布。通过双重免疫染色研究 HU-MSC 在宿主动物中的动态。通过 Q-PCR 和 ELISA 测量小脑组织和血清中的神经营养因子。我们的结果表明，HU-MSC 植入可显著改善应用后 8 周的共济失调小鼠的运动技能。HU-MSC 还减轻了治疗组的小脑萎缩和凋亡细胞数量。植入的 HU-MSC 至少在小脑内保留了 3 个月，没有明显分化。HU-MSC 治疗的小鼠在小脑提取物和血清中胰岛素样生长因子-1（IGF-1）和血管内皮生长因子（VEGF）的表达增强。双重免疫染色显示，一些 MAB1287 阳性细胞与 IGF-1 或 VEGF 表达细胞共定位。我们的结果表明，HU-MSC 治疗能够缓解共济失调小鼠模型的运动障碍和小脑萎缩，可能是通过促进特定的神经营养因子。
