Making Connections: Mesenchymal Stem Cells Manifold Ways to Interact with Neurons

Int J Mol Sci. 2022 May 21;23(10):5791. doi: 10.3390/ijms23105791.

Abstract

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.

Keywords: extracellular vesicles; gap junction; mesenchymal cells; neurons; tunneling nanotubes.

MeSH terms

  • Adult
  • Cell Communication
  • Cell Survival / physiology
  • Coculture Techniques
  • Humans
  • Mesenchymal Stem Cells*
  • Sensory Receptor Cells

Grants and funding

This research received no external funding.