Transient Cell-to-Cell Signaling Before Mitosis in Cultures of Human Bone Marrow-Derived Mesenchymal Stem/Stromal Cells

Some types of cells, if not all, that undergo signal exchanges in culture need to contact other cells for various reasons, such as cell-to-cell contact for growth inhibition. However, signal exchanges by cell-to-cell contact before proliferation have never been reported. Using time-lapse recording, we discovered the emergence of several astonishing cell-to-cell contact modes in bone marrow-derived mesenchymal stem/stromal cells (MSCs) before the cells divided. When the cells contacted with another, a huge temporary synapse-like structure formed for molecule exchanges; a cell-tissue particle was taken in by a recipient cell; two cell membranes formed infusion-like structure for a short time; and even a 20-μm long and 5-μm wide cell tail was grafted to another cell. A total of 87% of cells underwent cell-to-cell contact before dividing. After epidermal growth factor–green fluorescent protein (EGF-GFP) vectors were transfected into MSCs and the cells were cocultured with unmanipulated MSCs, the unmanipulated MSCs took in EGF-GFP particles from EGF-GFP expressed MSCs, immediately increased in mitogen genes, and then divided. These results suggest that cells which may lack signal molecules may need to obtain these molecules from other cells through various types of cell-to-cell contact, as mentioned above. Our study provided valuable information to better understand the behaviors of cell-to-cell contact and communication before mitosis.