Tunneling nanotubes mediate rescue of prematurely senescent endothelial cells by endothelial progenitors: exchange of lysosomal pool

摘要: Although therapeutic effect of adoptive transfer endothelial progenitor cells (EPC) has been well-substantiated, the actual engraftment is relatively low compared to a robust functional improvement vasculopathy. Cellular mechanisms governing this action remain elusive. A recently discovered cell-cell communication via tunneling nanotube (TNT) formation capable transferring mitochondria and lysosomes between – “organellar diakinesis”. Based on previous demonstration lysosomal dysfunction in exposed AGE-modified collagen I, we inquired whether TNT mechanism may be involved EPC-mediated repair stressed cells. Here demonstrate that EPC selectively multiplicatively establish with endothelia. The guidance cues for selectivity are provided by exofacially phosphatidylserine moieties. Lysosomal associated preservation pH gradient, functionally reconstituting pool improving cell viability, reducing premature senescence apoptosis. In vivo, streptozotocin-diabetic mice results TNT-dependent reduction senescent correction endothelium-dependent vasorelaxation. Collectively, these data selective multiplicative endothelia, reconstitution pool, improved viability function