Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis. Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis. Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay. Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas. Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

The aim of the study was to investigate the mechanisms of action of multipotent mesenchymal stromal cells (MMSCs) in a model of tetrachloromethane-induced liver fibrosis in mice. The experiments were performed on 50 mice. MSCs isolated from mouse placenta choriona were used in the study. MSCs were transplanted at a dose of 1 million cells into the tail vein. α-SMA, MMP-9, MMP 13, and TIMP-1 positive regions were analyzed by immunohistochemical method to evaluate the mechanisms of MMSCs action. Sirius red dye was used for connective tissue staining. HGF and TGF-β were determined by immunoassay in liver homogenate. We obtained that transplantation of MMSCs leads to a decrease in the area of α-SMA, TIMP-1 positive regions, an increase in the number of cells expressing MMP-9 and MMP 13. An increase in the level of hepatocyte growth factor and a decrease in transforming growth factor beta in liver homogenate after hMSCs transplantation in liver fibrosis was found. The results of the study demonstrated the efficacy of placental MMSCs in liver fibrosis. The antifibrotic mechanisms of action of hMSCs can include the ability to increase the expression of HGF, decrease the level of TGF-β, increase the production of matrix metalloproteinases-9 and -13, as well as the ability to inhibit the expression of tissue inhibitor of matrix metalloproteinases type 1.

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration.

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.