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Comparing the different response of PNS and CNS injured neurons to mesenchymal stem cell treatment
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2017-11-06 , DOI: 10.1016/j.mcn.2017.11.004
Marianna Monfrini , Maddalena Ravasi , Daniele Maggioni , Elisabetta Donzelli , Giovanni Tredici , Guido Cavaletti , Arianna Scuteri

Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking. Moreover, CNS and PNS neurons present many different biological properties, and it is still unclear if they respond in the same manner not only to MSC treatment, but also to injuries. For these reasons, in this study we compared the susceptibility of cortical and sensory neurons both to toxic drug exposure and to MSC action, in order to verify if these two neuronal populations can respond differently.

Our results demonstrated that Cisplatin (CDDP), Glutamate, and Paclitaxel-treated sensory neurons were protected by the co-culture with MSCs, in different manners: through direct contact able to block apoptosis for CDDP- and Glutamate-treated neurons, and by the release of trophic factors for Paclitaxel-treated ones. A possible key soluble factor for MSC protection was Glutathione, spontaneously released by these cells. On the contrary, cortical neurons resulted more sensitive than sensory ones to the toxic action of the drugs, and overall MSCs failed to protect them. All these data identified for the first time a different susceptibility of cortical and sensory neurons, and demonstrated a protective action of MSCs only against drugs in peripheral neurotoxicity.



中文翻译:

比较PNS和CNS损伤的神经元对间充质干细胞治疗的不同反应

间充质干细胞(MSCs)是成人骨髓来源的干细胞,实际上无差别地被提议用于治疗中枢(CNS)和周围神经系统(PNS)的神经系统疾病,作为能够通过多种途径治疗许多不同疾病的灵丹妙药它们的免疫调节能力和对神经元存活的支持作用。然而,尽管对于定义其真实和具体的作用是强制性的,但仍然缺乏对MSC在不同疾病中作用的确切机制的鉴定。此外,CNS和PNS神经元具有许多不同的生物学特性,目前尚不清楚它们是否以相同的方式不仅对MSC治疗而且对损伤都有反应。由于这些原因,在这项研究中,我们比较了皮质和感觉神经元对有毒药物暴露和对MSC作用的敏感性,

我们的研究结果表明,顺铂(CDDP),谷氨酸和紫杉醇治疗的感觉神经元通过与MSC的共培养以不同方式得到保护:通过直接接触能够阻断CDDP和谷氨酸治疗的神经元的凋亡,以及通过紫杉醇治疗的营养因子的释放。这些细胞自发释放的谷胱甘肽可能是保护MSC的关键可溶性因子。相反,皮质神经元对药物的毒性作用比感觉神经元敏感,并且整个MSC未能保护它们。所有这些数据首次确定了皮层和感觉神经元的敏感性,并证明了MSC仅对周围神经毒性药物具有保护作用。

更新日期:2017-11-06
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