Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Department of Health Science, Faculty of Medicine, University of Milan, Via A. di Rudinì 8, 20142 Milan, Italy.
Exp Neurol. 2014 Apr;254:121-33. doi: 10.1016/j.expneurol.2014.01.015. Epub 2014 Jan 29.
Spinal cord injury presents a significant therapeutic challenge since the treatments available are mostly vain. The use of stem cells to treat this condition represents a promising new therapeutic strategy; therefore, a variety of stem cell treatments have been recently examined in animal models of CNS trauma. In this work, we analyzed the effects of third trimester amniotic fluid cells in a mouse model of spinal cord injury. Among the different cultures used for transplantation, some were able to induce a significant improvement in motor recovery (cultures #3.5, #3.6 and #7.30), evaluated by means of open field free locomotion. All effective cell cultures expressed the surface marker nerve/glial antigen 2, ortholog of the human chondroitin sulfate proteoglycan 4, which is present on several types of immature progenitor cells. The improved motor functional recovery was correlated with higher myelin preservation in the ventral horn white matter and an increased vascularization in the peri-lesion area. Real-Time PCR analysis showed higher expression levels of vascular endothelial growth factor and hypoxia-inducible factor-1α mRNA two days after cells transplantation compared to PBS-treated animals, indicating that an angiogenic pathway might have been activated by these cells, possibly through the production of hepatocyte growth factor. This cytokine appears to be produced mostly in filtering organs, such as the lung, of the transplanted animals and is likely released in the blood suggesting an endocrine role of hepatocyte growth factor in targeting the injury site.
脊髓损伤是一个重大的治疗挑战,因为现有的治疗方法大多无效。干细胞用于治疗这种疾病代表了一种有前途的新治疗策略;因此,最近在中枢神经系统创伤的动物模型中检查了各种干细胞治疗方法。在这项工作中,我们分析了第三孕期羊水细胞在小鼠脊髓损伤模型中的作用。在用于移植的不同培养物中,一些培养物(#3.5、#3.6 和#7.30)能够通过开放场自由运动评估显著改善运动恢复。所有有效的细胞培养物均表达了神经胶质抗原 2 表面标志物,其为人软骨素硫酸蛋白聚糖 4 的同源物,存在于几种类型的未成熟祖细胞上。运动功能的改善恢复与腹角白质中髓鞘保存的增加以及损伤周围区域血管化的增加相关。实时 PCR 分析显示,与 PBS 处理的动物相比,细胞移植后两天血管内皮生长因子和缺氧诱导因子-1α mRNA 的表达水平更高,这表明这些细胞可能通过产生肝细胞生长因子激活了血管生成途径。这种细胞因子似乎主要在移植动物的过滤器官(如肺)中产生,并且可能在血液中释放,表明肝细胞生长因子在靶向损伤部位方面具有内分泌作用。