Apoptotic endothelial cells demonstrate increased adhesiveness for human mesenchymal stem cells

• Published in: Journal of cellular physiology 2009-04, Vol.219 (1), p.23-30
• Main Authors: Potapova, Irina A., Cohen, Ira S., Doronin, Sergey V.
• Format: Article
• Language: English
• Subjects: Androstadienes - pharmacology; Animals; Antigens, Surface - metabolism; Apoptosis - physiology; Cell Adhesion - physiology; Cells, Cultured; Cycloheximide - pharmacology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Enzyme Inhibitors - pharmacology; Humans; Interleukin-1beta - metabolism; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - physiology; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - physiology; NADH Dehydrogenase - metabolism; Okadaic Acid - pharmacology; Protein Synthesis Inhibitors - pharmacology; Signal Transduction - physiology; Staurosporine - pharmacology; Tumor Necrosis Factor-alpha - metabolism; von Willebrand Factor - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.21645

Mesenchymal stem cells (MSCs) participate in the wound healing process in mammalians. Adhesion of MSCs to endothelium is a key step in the homing of MSCs circulating in the bloodstream to the sites of injury and inflammation. Because endothelial cells (ECs) may become apoptotic under certain pro‐inflammatory conditions, we investigated the effects of pro‐inflammatory, TNF‐α and IL‐1β, and pro‐apoptotic agents, actinomycin D, cycloheximide, okadaic acid, wortmannin, and staurosporine, on human MSCs (hMSCs) adhesion to ECs. Treatment of ECs with pro‐apoptotic agents markedly increased adhesion of hMSCs to ECs. This adhesion correlated with reduction of mitochondrial membrane potential, inhibition of NADH dehydrogenases, and release of von Willebrand factor (vWF) by ECs. Treatment of ECs with exogenous vWF also stimulated hMSC adhesion. These data provide evidence that apoptosis of ECs may regulate homing of hMSCs to the sites of tissue injury. These results are consistent with the hypothesis that activation of apoptotic signaling pathways in ECs releases vWF which regulates hMSC adhesion to ECs. J. Cell. Physiol. 219: 23–30, 2009. © 2008 Wiley‐Liss, Inc.