Melatonin,tunneling nanotubes,mesenchymal cells,and tissue regeneration

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.

Super-resolution imaging of the dynamic cleavage of intercellular tunneling nanotubes

As a new method of cell-cell communication,tunneling nanotubes(TNTs)play important roles in cell-cell signaling and mass exchanges.However,a lack of powerful tools to visualize dynamic TNTs with high temporal/spatial resolution restricts the exploration of their formation and cleavage,hindering the complete understanding of its mechanism.Herein,we present the first example of using stochastic optical reconstruction microscopy(STORM)to observe the tube-like structures of TNTs linking live cells with an easily prepared fluorescent dye.Because of this new imaging microscopy,the cleavage process of TNTs was observed with a high spatial resolution.

Tunneling nanotubes between rat primary astrocytes and C6 glioma cells alter proliferation potential of glioma cells

The tunneling nanotube （TNT） is a newly discovered, long and thin tubular structure between cells. In this study, we established a co-culture system for rat primary astrocytes and C6 glioma cells and found that TNTs formed between them. Most of the TNTs initiated from astrocytes towards C6 glioma cells. The formation of TNTs depended on p53. In addition, hydrogen peroxide increased the number of TNTs in the co-culture system. Established TNTs reduced the proliferation of C6 glioma cells. Our data suggest that TNTs between astrocytes and glioma cells facilitate substance transfer and therefore alter the properties, including the proliferation potential, of glioma cells.