Experimental Neurology Unit and Milan Center for Neuroscience, School of Medicine and Surgery, Milano-Bicocca University, 20900 Monza, Italy.
Int J Mol Sci. 2022 May 21;23(10):5791. doi: 10.3390/ijms23105791.
Mesenchymal Stem Cells (MSCs) are adult multipotent cells able to increase sensory neuron survival: direct co-culture of MSCs with neurons is pivotal to observe a neuronal survival increase. Despite the identification of some mechanisms of action, little is known about how MSCs physically interact with neurons. The aim of this paper was to investigate and characterize the main mechanisms of interaction between MSCs and neurons. Morphological analysis showed the presence of gap junctions and tunneling nanotubes between MSCs and neurons only in direct co-cultures. Using a diffusible dye, we observed a flow from MSCs to neurons and further analysis demonstrated that MSCs donated mitochondria to neurons. Treatment of co-cultures with the gap junction blocker Carbenoxolone decreased neuronal survival, thus demonstrating the importance of gap junctions and, more in general, of cell communication for the MSC positive effect. We also investigated the role of extracellular vesicles; administration of direct co-cultures-derived vesicles was able to increase neuronal survival. In conclusion, our study demonstrates the presence and the importance of multiple routes of communication between MSCs and neurons. Such knowledge will allow a better understanding of the potential of MSCs and how to maximize their positive effect, with the final aim to provide the best protective treatment.
间充质干细胞（MSCs）是一种能够增加感觉神经元存活的成人多能细胞：MSCs 与神经元的直接共培养对于观察神经元存活增加至关重要。尽管已经确定了一些作用机制，但对于 MSCs 如何与神经元物理相互作用知之甚少。本文的目的是研究和表征 MSCs 和神经元之间的主要相互作用机制。形态分析显示，只有在直接共培养物中才存在 MSCs 和神经元之间的缝隙连接和隧道纳米管。使用可扩散染料，我们观察到从 MSCs 到神经元的流动，进一步的分析表明 MSCs 将线粒体捐赠给神经元。用缝隙连接阻断剂 Carbenoxolone 处理共培养物会降低神经元的存活率，从而证明了缝隙连接以及更普遍的细胞通讯对于 MSC 积极作用的重要性。我们还研究了细胞外囊泡的作用；给予直接共培养衍生的囊泡能够增加神经元的存活率。总之，我们的研究表明 MSCs 和神经元之间存在多种通讯途径，并且这些途径非常重要。这些知识将有助于更好地理解 MSCs 的潜力以及如何最大限度地发挥其积极作用，最终目标是提供最佳的保护治疗。
