Mitochondrial Donation As a Mechanism of Participation of Mesenchymal Stromal Cells in Regenerative Processes

Abstract

Mesenchymal stromal cells (MSCs) are universal regulators of regenerative processes due to their ability to paracrine release of regulatory molecules or to replace dead cells by differentiation in the appropriate direction. Recently, another mechanism for the beneficial effects of MSCs on damaged tissues has been discovered, namely transfer of mitochondria into its cells in response to stress signals. MSCs can transfer mitochondria through tunnel nanotubes forming a connecting bridge between cells, through gap junctions, by release as part of extracellular vesicles or in the free form, as well as by complete or partial fusion with recipient cells. In the damaged cells that received mitochondria from MSCs, the disturbed energy metabolism is restored and oxidative stress is reduced, which is accompanied by increased survival, and in some cases also by increased proliferation or changes in differentiation status. Restoration of energetics after mitochondria transfer from MSCs has a beneficial effect on functional activity of recipient cells and promotes suppression of inflammatory reactions. It has been repeatedly demonstrated on models of damage of various organs in experimental animals that the transfer of mitochondria from MSCs to target cells makes a significant contribution to the therapeutic efficacy of MSCs. Therefore, methods to enhance mitochondrial donation are currently being searched for. However, it should be taken into account that MSCs are able to transfer mitochondria to malignant cells, thus stimulating tumor growth and increasing its resistance to chemotherapy. These data make us cautious about the prospects of using MSCs in cell therapy, but, on the other hand, they can serve as a basis for searching for new therapeutic targets in the treatment of cancer.