Abstract: Endoglin (CD105) is one of the major marker antigens of mesenchymal stem cells (MSC) and endothelial cells. While the functions of endoglin in endothelial cells have been widely declared, little is known about its role in MSC biology. Here, we present a comparative study of CD105 expression, interna-lization and shedding by human endothelial cell line EA.hy926 and human adipose tissue-derived MSC from various sources. While the fraction of CD105-positive cells in all MSC cultures and EA.hy926 endothelial cells was consistently high, over 97% of the population, the density of CD105 molecules on the surface of MSC isolated from visceral and subcutaneous adipose tissue was substantially different. The total expression level of endoglin mRNA in MSC and endothelial cells was similar, whereas the contribution of the transcripts that yield a short CD105 isoform was higher in endothelial cells. Using a set of monoclonal antibodies (mAbs) directed against different endoglin epitopes, we revealed significant differences in the dynamics of CD105 metabolism on the membranes of endothelial cells and MSC. On EA.hy926 endothelial cells, CD105 molecules bound with antibodies were internalized and remained in the perinuclear space. In MSC cultures, on the contrary, the CD105-mAbs complexes were not subjected to endocytosis and remained on the cell membrane for a long time. We demonstrated that MSC, similarly to the endothelial cells, do shed the extracellular endoglin fragment into the environment as a soluble CD105 isoform. The shedding process in MSC was, however, substantially less intensive compared with the endothelial cells. Thus, we revealed, for the first time, that in MSC, unlike the endothelial cells, endoglin persists on cell surface for a long time and is not interna-lized after binding with antibodies. Endoglin shedding from MSC surface and the concomitant generation of the soluble endoglin form were also demonstrated for the first time.