The Effect of Autophagy Modeling in Stem Cells on the Regeneration of Myeloid Tissue in Mice after Their Sublethal Irradiation

Introduction. Acute radiation disease is one of the urgent problems of modern medicine. The new approach using mesenchymal stem cells (MSCs) show its effectiveness. Results of MSC therapy is contradictory and requires further researches to assess the production of hematopoiesis-inducing growth factors and the level of hematopoiesis activation.

The purpose of the study was modeling of autophagy process with estimation of the degree of hematopoiesis restoration using modulated MSCs.

Materials and methods. The experiment was carried out on 60 outbred mice. Animals were exposed to ionizing radiation (IR) with transplantation of modulated and unmodulated MSCs to analyze reticulocyte, leukocyte formula, bone marrow with myelogram counting and enzyme immunoassay. Statistical analysis was performed using IBM SPSS Statistics 27 program.

Results and discussion. After IR exposure, a decreased in lymphoid (–45.0 %), neutrophilic (–19.5 %) and megakaryocyte lineages (–52.2 %) was noted. Expression of SCF and Flt3-ligand was higher in the MSC + trehalose group compared to rapamycin by 16.3 % and 19.7 %. Using MSCs increased bone marrow cellularity by +11.1 % due to neutrophilic and lymphoid cells. MSC with activated mTOR-independent autophagy increased in bone marrow cellularity among the studied groups: lymphocytes +12.9 %, megakaryocytes +15.2 %. Inhibition of autophagy in MSC decreased numbers of myelokaryocytes (–8.7 %), neutrophilic (–14.5 %) and lymphoid (–9.8 %) cells.

Conclusion. The use of MSCs with activated mTOR-independent autophagy has a greater therapeutic potential in the restoration of hematopoiesis. Inhibition of autophagy in MSCs worsens their biological properties in terms of growth factor production and myeloid tissue regeneration after IR exposure.

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