Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Stem Cells Transl Med. 2017 Feb;6(2):634-646. doi: 10.5966/sctm.2016-0071. Epub 2016 Sep 22.
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD. Stem Cells Translational Medicine 2017;6:634-646.
过去十年的研究强烈表明，间充质干细胞（MSC）介导的治疗益处主要归因于其分泌组，分泌组被提议作为治疗帕金森病（PD）的一种可能治疗工具。事实上，已经表明 MSC 分泌组增加了神经发生和细胞存活，并在不同条件下具有多种神经保护作用。此外，使用动态培养条件（通过计算机控制的生物反应器）可以进一步调节 MSC 分泌组，从而产生更有效的神经营养因子鸡尾酒（即条件培养基）。在这项研究中，我们通过基于蛋白质组学的分析来描述 MSC 分泌组，研究其对 6-羟基多巴胺（6-OHDA）PD 大鼠模型生理恢复的治疗效果。为此，我们将 MSC 分泌组注入黑质（SNc）和纹状体（STR），对注射动物与未处理组的行为表现进行特征描述，并确定组织学参数。我们观察到，分泌组增强了 SNc 和 STR 中多巴胺能神经元（即酪氨酸羟化酶阳性细胞）和神经元末梢的增加，从而支持帕金森大鼠运动表现结果（通过旋转棒和阶梯试验评估）的恢复。最后，通过联合质谱分析和 Bioplex 分析对 MSC 分泌组进行蛋白质组学表征，揭示了存在重要的神经调节分子，即胱抑素 C、胶质衍生的神经素、半乳糖凝集素-1、色素上皮衍生因子、血管内皮生长因子、脑源性神经营养因子、白细胞介素-6 和胶质细胞系衍生的神经营养因子。总的来说，我们得出结论，单独使用人 MSC 分泌组能够部分逆转 6-OHDA PD 动物的运动表型和神经元结构。这表明人 MSC 分泌组可能代表治疗 PD 的一种新的治疗方法。《干细胞转化医学》2017 年；6：634-646.
Zotero 插件
