Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
J Proteomics. 2013 Dec 6;94:437-50. doi: 10.1016/j.jprot.2013.06.008. Epub 2013 Jun 17.
Multiple sclerosis (MS) is a chronic inflammatory and progressive disorder of the central nervous system (CNS), which ultimately causes demyelination and subsequent axonal injury. Experimental autoimmune encephalomyelitis (EAE) is a well-characterized animal model to study the etiology and pathogenesis of MS. This model can also be used to investigate various therapeutic approaches for MS. Herein; we have treated a score 3 EAE mouse model with an embryonic stem cell-derived neural precursor. Clinical analysis showed recovery of the EAE model of MS following transplantation. We analyzed the proteome of spinal cords of healthy and EAE samples before and after transplantation. Proteome analysis revealed that expressions of 86 spinal cord protein spots changed in the EAE or transplanted mouse compared to controls. Mass spectrometry resulted in identification of 72 proteins. Of these, the amounts of 27 differentially expressed proteins in EAE samples returned to sham levels after transplantation, suggesting a possible correlation between changes at the proteome level and clinical signs of EAE in transplanted mice. The recovered proteins belonged to various functional groups that included disturbances in ionic and neurotransmitter release, apoptosis, iron hemostasis, and signal transduction. Our results provided a proteomic view of the molecular mechanisms of EAE recovery after stem cell transplantation.
In this study, we applied proteomics to analyze the changes in proteome pattern of EAE mouse model after embryonic stem cell-derived neural precursor transplantation. Our proteome results clearly showed that the expression levels of several differentially expressed proteins in EAE samples returned to sham levels after transplantation, which suggested a possible correlation between changes at the proteome level and decreased clinical signs of EAE in transplanted mice. These results will serve as a basis to address new questions and design new experiments to elucidate the biology of EAE and recovery after transplantation. A thorough understanding of stem cell-mediated therapeutic mechanisms might result in the development of more efficacious therapies for MS than are currently available.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症和进行性疾病，最终导致脱髓鞘和随后的轴突损伤。实验性自身免疫性脑脊髓炎（EAE）是一种研究 MS 病因和发病机制的成熟动物模型。该模型还可用于研究 MS 的各种治疗方法。在此，我们用胚胎干细胞衍生的神经前体细胞治疗了评分 3 的 EAE 小鼠模型。临床分析显示，移植后 MS 的 EAE 模型得到恢复。我们分析了健康和 EAE 样本在移植前后脊髓的蛋白质组。蛋白质组分析显示，与对照组相比，EAE 或移植小鼠的 86 个脊髓蛋白点的表达发生了变化。质谱分析导致鉴定出 72 种蛋白质。其中，27 种差异表达蛋白在 EAE 样本中的含量在移植后恢复到假手术水平，这表明在移植小鼠中，蛋白质组水平的变化与 EAE 的临床症状之间可能存在相关性。恢复的蛋白质属于各种功能组，包括离子和神经递质释放、细胞凋亡、铁止血和信号转导的紊乱。我们的结果提供了 EAE 后干细胞移植恢复的分子机制的蛋白质组学观点。
在这项研究中，我们应用蛋白质组学分析了胚胎干细胞衍生的神经前体细胞移植后 EAE 小鼠模型蛋白质组模式的变化。我们的蛋白质组结果清楚地表明，EAE 样本中几种差异表达蛋白的表达水平在移植后恢复到假手术水平，这表明蛋白质组水平的变化与移植小鼠 EAE 临床症状的减少之间可能存在相关性。这些结果将为解决新问题和设计新实验提供基础，以阐明 EAE 和移植后恢复的生物学。对干细胞介导的治疗机制的深入了解可能会导致开发出比目前更有效的 MS 治疗方法。
