Apoptotic endothelial cells demonstrate increased adhesiveness for human mesenchymal stem cells.
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-alpha and IL-1 beta, 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.
Potapova
Irina A
IA
Department of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Cohen
Ira S
IS
Doronin
Sergey V
SV
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin; D014841:von Willebrand Factor / Q000378:metabolism
D000730:Androstadienes; D000954:Antigens, Surface; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D019319:Okadaic Acid; D003513:Cycloheximide; D009245:NADH Dehydrogenase; D019311:Staurosporine; D000077191:Wortmannin