Digoxin as a Cardiac Glycosoids induced Apoptosis in Mesenchymal Stem Cells: an in Vitro Study

Low number of engrafted cells is the main challenge in stem cell therapy. The cells should overcome with reactive oxygen species, food deprivation and toxicity of the pharmacological agents that patients take during their treatment. As an example, cardiac glycosides such as digoxin can inhibit the cell proliferation and lead to apoptosis. Therefore, in this study, we are trying to know stem cell behavior following digoxin treatment. Mesenchymal Stem Cells were treated with different concentrations of digoxin for 6, 12, 24 and 48 hours. Cell viability was detected with trypan blue. Hoechst staining and tunnel assay were conducted to evaluate nuclear configuration and apoptosis in MSCs. Cell viability decreased after digoxin treatment in all groups during 6, 12, 24 and 48h significantly (P<0.05). After 6 hours, rate of nuclear fragmentation was significantly higher in30 and 40μM digoxin than control group (P< 0.001). Treatment with 20, 30 and 40μM digoxin led to nuclear damage significantly compare to control group after 12h (P< 0.001). Also, after 24 and 48 hours, nuclear damage significantly increased in 15, 20, 30 and 40μM of digoxin (P< 0.001).Digoxin induced apoptosis significantly in all groups in time and dose dependent, so that the highest rate of cell death was found after 48h.It is suggested that digoxin might lead to decline in cell survival and increase cell apoptosis in a dose and time dependent and interfere with stem cell therapy. Therefore, it is recommended to consider application of glycosides in concurrence with stem cell therapy.