Department of Neurology, Medical University of Lodz, 90-419 Lodz, Poland.
Department of Immunogenetics, Medical University of Lodz, 90-419 Lodz, Poland.
Int J Mol Sci. 2022 Feb 16;23(4):2177. doi: 10.3390/ijms23042177.
Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton's jelly (WJ-MSCs) make them an interesting research and therapeutic model. Most WJ-MSCs transplants for multiple sclerosis use intrathecal administration. We studied the effect of cerebrospinal fluid (CSF) obtained from MS patients on the secretory activity of WJ-MSCs and broaden this observation with WJ-MSCs interactions with human oligodendroglia cell line (OLs). Analysis of the WJ-MSCs secretory activity with use of Bio-Plex Pro™ Human Cytokine confirmed significant and diverse immunomodulatory potential. Our data reveal rich WJ-MSCs secretome with markedly increased levels of IL-6, IL-8, IP-10 and MCP-1 synthesis and a favourable profile of growth factors. The addition of MS CSF to the WJ-MSCs culture caused depletion of most proteins measured, only IL-12, RANTES and GM-CSF levels were increased. Most cytokines and chemokines decreased their concentrations in WJ-MSCs co-cultured with OLs, only eotaxin and RANTES levels were slightly increased. These results emphasize the spectrum of the immunomodulatory properties of WJ-MSCs and show how those effects can be modulated depending on the transplantation milieu.
多发性硬化症(MS)是一种自身免疫性病因的神经疾病。使用间充质干细胞(MSCs)的实验疗法作为对新治疗选择的未满足需求的回应而出现。从 Wharton 胶(WJ-MSCs)获得的干细胞的独特免疫调节特征使它们成为一个有趣的研究和治疗模型。大多数多发性硬化症的 WJ-MSCs 移植都采用鞘内给药。我们研究了来自 MS 患者的脑脊液(CSF)对 WJ-MSCs 分泌活性的影响,并通过 WJ-MSCs 与人类少突胶质细胞系(OLs)的相互作用扩展了这一观察。使用 Bio-Plex Pro™人细胞因子分析 WJ-MSCs 的分泌活性证实了其具有显著且多样化的免疫调节潜力。我们的数据揭示了丰富的 WJ-MSCs 分泌组,其中 IL-6、IL-8、IP-10 和 MCP-1 的合成水平显著增加,并且生长因子的水平也很有利。将 MS CSF 添加到 WJ-MSCs 培养物中导致所测量的大多数蛋白质耗竭,只有 IL-12、RANTES 和 GM-CSF 水平增加。大多数细胞因子和趋化因子在与 OL 共培养的 WJ-MSCs 中的浓度降低,只有嗜酸性粒细胞趋化因子和 RANTES 水平略有增加。这些结果强调了 WJ-MSCs 免疫调节特性的范围,并显示了这些效应如何根据移植环境进行调节。