Effects of autophagy modulators on the therapeutic efficacy of multipotent mesenchymal stromal cells

Restoring damaged tissues and organs, particularly in cases of acute radiation injury, remains one of the major challenges in regenerative medicine. Acute radiation syndrome caused by high-dose ionizing radiation exposure is associated with profound suppression of hematopoiesis and damage to the bone marrow stroma. Multipotent mesenchymal stromal cells are regarded as a promising therapeutic tool because of their differentiation potential, immunomodulatory properties, secretion of trophic factors, and ability to support the hematopoietic niche. However, their clinical efficacy is limited by low survival under conditions of oxidative stress and inflammation. Mechanisms that increase the resistance of multipotent mesenchymal stromal cells to damaging factors and enhance their regenerative potential remain insufficiently studied. This work reviews current data on the role of autophagy—an evolutionarily conserved process of intracellular renewal—as a potential approach to increasing the functional activity of multipotent mesenchymal stromal cells. Pharmacologic strategies for autophagy modulation are discussed, including mTOR-dependent (sirolimus) and mTOR-independent (lithium, trehalose) approaches, as well as their effects on the survival, migration, and secretory activity of multipotent mesenchymal stromal cells. Particular attention is given to cell preconditioning as a strategy to enhance therapeutic efficacy in radiation injury. Available evidence supports the use of targeted autophagy activation as a key component in the development of standardized next-generation cell-based products capable of not only supporting but also actively restoring hematopoiesis after acute radiation exposure.