Adenosine-5'-triphosphate suppresses proliferation and migration capacity of human endometrial stem cells

Abstract

Extracellular ATP through the activation of the P2X and P2Y purinergic receptors affects the migration, proliferation and differentiation of many types of cells, including stem cells. High plasticity, low immunogenicity and immunomodulation ability of mesenchymal stem cells derived from human endometrium (eMSCs) allow them to be considered a prominent tool for regenerative medicine. Here, we examined the role of ATP in the proliferation and migration of human eMSCs. Using a wound healing assay, we showed that ATP-induced activation of purinergic receptors suppressed the migration ability of eMSCs. We found the expression of one of the ATP receptors, the P2X₇ receptor in eMSCs. In spite of this, cell activation with specific P2X₇ receptor agonist, BzATP did not significantly affect the cell migration. The allosteric P2X₇ receptor inhibitor, AZ10606120 also did not prevent ATP-induced inhibition of cell migration, confirming that inhibition occurs without P2X₇ receptor involvement. Flow cytometry analysis showed that high concentrations of ATP did not have a cytotoxic effect on eMSCs. At the same time, ATP induced the cell cycle arrest, suppressed the proliferative and migration capacity of eMSCs and therefore could affect the regenerative potential of these cells.

Keywords: Ca2+ influx; cell cycle; cell migration; endometrial stem cells; extracellular ATP; receptor P2X7.