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

Mesenchymal stem cells (MSCs) are obtained from different adult tissues but most commonly from adipose tissue and the bone marrow. Previous studies have shown that MSCs can also be isolated from the human endometrium and it has an important role in the endometrium’s cyclic regeneration. Endometrial stem cells (eMSCs) can be transformed into cells of the tissues of both the mesodermal and ectodermal rows. They also have a high availability, high level of plasticity, genome stability and high proliferative activity. These qualities make eMSCs important components of cell therapy for various diseases.

Adenosine-5′-triphosphate (ATP) is a nucleotide with multiple functions and a source of intracellular energy. ATP acts as a neurotransmitter and is secreted from many cells by exocytosis. Outside the cell, ATP serves as a signaling molecule and on the cell membrane; it binds to purinergic receptors P2X or P2Y. This process triggers a chain of other events that have an effect on important functions of different cells types and tissues. Recently, extracellular ATP has been found to affect the ability of healthy and cancer cells to migrate, which suggests that purine receptors play an important role in cancer invasion or metastasis. The migrating capacity of stem cells to specific tissues and organs is important for the morphogenesis, homeostasis and repair of normal tissues, and for the development of regenerative medicines based on stem cells.

By studying the role of extracellular ATP in the ability of eMSCs to proliferate and migrate, Dr Svetlana Semenova, Dr Alla Shatrova, Dr Irina Vassilieva, Dr Margarita Shamatova, Dr Natalja Pugovkina and Dr Yuri Negulyaev (all from the Institute of Cytology of the Russian Academy of Science) demonstrated that the activation of purinergic receptors by ATP reduces the capacity of eMSCs to migrate, and that ATP significantly inhibits cell growth by causing eMSCs accumulation in GO/G1 phase. The study is published in the Journal Cellular Molecular Medicine.

The Russian research team have found the endogenous expression of the P2X7R, an ATP receptor in eMSCs. However, by using BzATP (a specific P2X7 receptor agonist for cell activation) they have showed that P2X7R activation had no effect on cell migration. Furthermore, AZ10606120; the allosteric inhibitor of P2X7 receptor did not prevent ATP from suppressing cell migration. The authors concluded that the P2X7 receptor plays no significant role in  eMSCs migration.

Using FACS analysis authors found that high concentrations of ATP had no toxic effect on eMSCs. However, ATP caused the arrest of cell cycle and prevented the proliferation of eMSCs, therefore inducing the suppression the migration capacity of these cells. Consequently, ATP had the potential to affect the regenerative ability of eMSCs.

In summary, Dr Svetlana Semenova and her colleagues were able to demonstrate that the suppression of eMSCs proliferation by the effect of ATP resulted in a reduction in the migration ability of these cells. They recommended further studies are required to identify the specific mechanism of action of ATP on eMSCs. They also suggested that future studies that monitor how ATP regulates the proliferation and migration of eMSCs would provide information essential in improving the regenerative capacity of eMSCs for better use in regenerative medicine and tissue engineering.

This research was supported by grant of the Russian Science Foundation (RSF № 18-15-00106).