Farinazzo Alessia, Turano Ermanna, Marconi Silvia, Bistaffa Edoardo, Bazzoli Elena, Bonetti Bruno
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Cytotherapy. 2015 May;17(5):571-8. doi: 10.1016/j.jcyt.2015.01.005. Epub 2015 Mar 3.
Adipose-derived mesenchymal stromal cells (ASC) are known to promote neuroprotection and neuroregeneration in vitro and in vivo. These biological effects are probably mediated by paracrine mechanisms. In recent years, nanovesicles (NV) and microvesicles (MV) have been shown to play a major role in cell-to-cell communication. We tested the efficacy of NV and MV obtained from ASC in mediating neuroprotection and neuroregeneration in vitro.
We exposed neuronal cells (both cell line and primary cultures) to oxidative stress in the presence or not of NV or MV.
In this experimental setting, we found that low doses of NV or MV protected neurons from apoptotic cell death. We then assessed the neuroregenerative effect of NV/MV in cerebellar slice cultures demyelinated with lysophosphatidylcholine. We observed that low but not higher doses of NV and MV increased the process of remyelination and activated nestin-positive oligodendroglial precursors.
Taken together, our data in vitro support the relevance of ASC vesicles as a source of protecting and regenerating factors that might modulate the microenvironment in neuro-inflammatory as well as in neurodegenerative disorders. The present findings may suggest that stromal cell-derived vesicles might represent a potential therapeutic tool, enabling the safe administration of stromal cell effector factors, avoiding the cellular counterpart.
已知脂肪来源的间充质基质细胞(ASC)在体外和体内均可促进神经保护和神经再生。这些生物学效应可能是由旁分泌机制介导的。近年来,纳米囊泡(NV)和微囊泡(MV)已被证明在细胞间通讯中起主要作用。我们测试了从ASC获得的NV和MV在体外介导神经保护和神经再生的功效。
我们将神经元细胞(细胞系和原代培养物)在有或没有NV或MV的情况下暴露于氧化应激。
在该实验环境中,我们发现低剂量的NV或MV可保护神经元免于凋亡性细胞死亡。然后,我们评估了NV/MV在经溶血磷脂酰胆碱脱髓鞘的小脑切片培养物中的神经再生作用。我们观察到低剂量而非高剂量的NV和MV增加了髓鞘再生过程并激活了巢蛋白阳性少突胶质前体细胞。
综上所述,我们的体外数据支持ASC囊泡作为保护和再生因子来源的相关性,这些因子可能调节神经炎症和神经退行性疾病中的微环境。目前的研究结果可能表明,基质细胞衍生的囊泡可能代表一种潜在的治疗工具,能够安全地施用基质细胞效应因子,避免细胞对应物。