scholarly journals The effects of the transplantation of thymus-derived multipotent stromal cells on the immune system and survival of lethally irradiated mice

2018 ◽  
Vol 6 (2) ◽  
Author(s):  
K. Nikolska
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Stromal Cells ◽  
Multipotent Stromal Cells ◽  
Hematopoietic Stem ◽  
New Methods ◽  
Cell Transplants ◽  
Factor Α ◽  
Radioprotective Properties ◽  
Necrosis Factor

The traditional source for regeneration of the immune system is hematopoietic stem cells. Multipotent stromal cells (MSCs), especially MSCs of the thymus, have been significantly less studied for this purpose.The aim was to study the regenerative, immunobiological and radioprotective properties of thymus-derived multipotent stromal cells.Materials and methods. Researches were conducted to study the effect of transplantation of thymus-derived MSCs on the survival and features of restoration of the immune system of lethally irradiated mice. Lethally irradiated (with dose 9 Gy) CBA mice, 5-6 weeks old, were injected intravenously with 5·104 thymus-derived MSCs. On the 30th day the cellularity of lymphoid organs, bone marrow and blood, natural and adaptive immunity were studied.Results. It was found that transplanted thymus-derived MSCs significantly prolonged the survival and average lifespan of mice, restored the cellularity of bone marrow, the ability of bone marrow stromal cells to form fibroblast colonies, greatly increased the cellularity of the thymus and contributed to the normalization of the number of leukocytes in the blood. In addition, the natural cytotoxic activity of splenocytes and their ability to synthesize α/β- and γ-interferons, significantly increased, the number of antibody-producing cells was stimulated and the synthesis of antibodies increased. The concentration of the tumor necrosis factor α in the blood was significantly reduced.Conclusions. The results indicate that thymus-derived MSCs possess pronounced regenerative and immunobiological activity, which provides these cells with radioprotective ability. The obtained data can be used to develop combined cell transplants and new methods for improving their regenerative potential and radioprotective effects.

scholarly journals The effects of co-transplantation of bone marrow hematopoietic stem cell and thymic multipotent stromal cells on the immune system of mice during its regeneration after cyclophosphamide treatment

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
D. Demchenko ◽  
I. Nikolskiy
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Activity Level ◽  
Delayed Type Hypersensitivity ◽  
Blast Transformation ◽  
Multipotent Stromal Cells ◽  
Hematopoietic Stem ◽  
Stimulation Of

The multipotent stromal cells (MSCs) are considered as one of the most promising agents for regenerating the immune system due to its powerful secretion of reparative factors and immunomodulatory properties.The purpose of the study is to investigate the effect of co-transplantation of bone marrow hematopoietic stem cells (HSCs) and thymic multipotent stromal cells (MSCs) on regeneration of murine immune system damaged by cyclophosphamide.Materials and methods. MSCs were obtained from thymuses of C57BL mice using explant technique. Bone marrow cells (BMCs) were obtained by flushing out the femur with nutrient medium. The immune deficiency of mice was modelled by the treatment with cyclophosphamide. After that, the cells were co-transplanted and the parameters of the immune system was evaluated. We determined the total number of erythrocytes, hematocrit, and hemoglobin concentration in peripheral blood; phases of the cell cycle and apoptosis of the cells of the mesenteric lymph nodes; the number of antibody-producing cells in the spleen; delayed type hypersensitivity (DTH); proliferative and cytotoxic activity of natural killer lymphocytes; phagocytic activity, level of spontaneous and induced bactericidal activity of peritoneal macrophages.Results. It was shown that in contrast to BMCs, the use of MSCs alone or co-transplantation of these cells increased the spontaneous proliferative activity of lymphocytes with a significant decrease in the number of lymph node cells in G0/G1 phase by 9.2 % and an increase in the number of lymphocytes in G2-M+S phase by 35 %, as well as restoring cellularity of bone marrow, thymus and lymph nodes in mice treated with cyclophosphamide. Regeneration of erythropoiesis was stimulated by BMCs, which was manifested by the normalization of hematocrit and hemoglobin, and an increase in the number of reticulocytes in the blood by 2.2 times compared with the group of mice receiving cyclophosphamide. Co-transplantation had less pronounced, but similar effect. Transplantation of thymic MSCs stimulated the natural cytotoxicity of splenocytes by 2.7 times and substantially increased the number of antibody-producing cells in the spleen by 1.7 times compared with the group of mice receiving cyclophosphamide. Co-transplantation had a pronounced suppressive effect on the blast transformation reaction induced by phytohemagglutinin by 1.7 times, but showed a stimulating effect on DTH response by 1.46 times. Transplantation of BMCs did not affect the functional activity of the immune system.Conclusion. The effects of co-transplantation of BMCs and thymic MSCs are realized in the several parts: stimulation of hematological parameters recovery (like under the effect of BMCs separately), normalization of cell number of lymphoid organs (as under the impact of thymic MSCs); inhibition of blast transformation activity and stimulation of DTH are the effects of co-transplantation.

scholarly journals Comparison of the effects of co-transplantation of bone marrow hematopoietic stem cells and thymic multipotent stromal cells on the immune system of mice depending on methods

2021 ◽  
pp. 3-11
Author(s):  
Dariia Demchenko ◽  
Igor Nikolskiy ◽  
Valentyna Nikolskaya ◽  
Natalia Pelykh
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune System ◽  
Hematopoietic Stem Cells ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Suppressive Effect ◽  
Multipotent Stromal Cells ◽  
Hematopoietic Stem ◽  
Marrow Cells

Physical interaction of multipotent stromal cells (MSCs) and hematopoietic stem cells (HSCs) is a modern approach to effective and focused changes in the properties of HSCs. Resulting of those contact interaction is significant activation of cells with following immune system restoration. The purpose of the study is to investigate the effect of co-transplantation of bone marrow hematopoietic stem cells (HSCs) and thymic multipotent stromal cells (MSCs) separately and as a union of cells on regeneration of the murine immune system, damaged by cyclophosphamide. MSCs were obtained from thymuses of C57BL mice using explant technique. Bone marrow cells (BMCs) were obtained by flushing out the femur with a nutrient medium. BMCs were cocultivated for 2 hours on the monolayer of thymus-derived MSCs. The immune deficiency of mice was modelled by the treatment with cyclophosphamide (CP). After that, the cells were co-transplanted in two methods (separately into different the retroorbital sinus and as a union after co-cultivation) and the parameters of the immune system were evaluated. It was shown, that separate co-transplantation of BMCs and thymus-derived MSCs is associated with the restoration of the number of bone marrow cells, thymus, spleen and lymph nodes with an increase in the proliferation index of lymph node cells by 1.4 times compared to control. It normalized the previous reduced concentration of hemoglobin and hematocrit in the blood. Co-transplantation had a suppressive effect on the blast transformation reaction, induced by phytohemagglutinin, by 4.3 times, but showed a stimulating effect on DTHR response by 1.6 times compared to control. Co-transplantation of the union of BMCs and MSCs is associated with the restoration of the number of bone marrow cells, spleen and lymph nodes. The level of spontaneous apoptosis of lymph node cells significantly increased by 3.3 times compared to control. It had not effect on hematological parameters, but is activated to impact the immune system. Thus, as a result of cells union administration showed normalization of the bactericidal activity of peritoneal macrophages, unlike the separate co-transplantation. This cells graft had a suppressive effect on the number of antibody-producing cells in the spleen by 4.2 times compared to control. Previous co-cultivation and contact interaction of cells change the properties of cell graft. The effect of co-transplantation of BMCs and thymic MSCs is not a simple additive effect of cells. It is acquiring the features typical to certain cell types, and the expression of new characteristics. We assume this phenomenon as a result development of complex cells cooperative processes in vivo and in vitro

scholarly journals Suppression of gastric ulcers formation under immobilization water-immersion stress by preliminary transplantating the multipotent stromal cells

2019 ◽  
Vol 79 (3) ◽  
pp. 72-78
Author(s):  
Y.-M. Semenova ◽  
I. Nikolsky ◽  
L. Ostapchenko
Keyword(s):  
Bone Marrow ◽  
Gastric Ulcer ◽  
Immune System ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Water Immersion ◽  
Ulcer Formation ◽  
Multipotent Stromal Cells ◽  
Prolonged Stress

To investigate the effect of pre-transplantation of multipotent stromal cells (MSCs) of bone marrow on gastric ulcer formation and the state of the immune system in conditions of acute and prolonged stress. Wistar rats reproduced immobilizing water-immersion stress of 2 types: acute and prolonged. Investigated the number and area of stress ulcers, thymus and spleen, as well as hematologic parameters, proliferative and cytotoxic activity of peripheral blood mononuclear cells, splenocytes and cells of lymph nodes, determined the absorption activity of neutrophils. With prolonged stress as a result of MSC transplantation, the number and area of ulcers significantly decreased, indicating the adaptive protective effect of cells. With acute stress, the introduction of MSC had virtually no effect on ulcer formation. With prolonged stress, there was a decrease in thymus, spleen and leukocyte counts in the blood. Under the influence of transplanted MSCs, the number of all mobilized cells was normalized with the exception of lymphocytes. The natural cytotoxicity and proliferative activity of splenocytes, cells of lymph nodes and peripheral blood in acute and prolonged stress as a result of the introduction of MSC did not change significantly. The introduction of bone marrow MSС 24 h before the last reproduction of stress responses in the model of prolonged stress significantly reduced the number and area of ulcers, which generally indicates the anti-ulcer effect of cells, and normalized the stress-induced quantitative cellular changes in the immune system. Transplantation of bone marrow MSCs to rats prior to reproduction of stress enhances the adaptive antistress mechanisms that develop during prolonged stress, leading to suppression of gastric ulcer formation and significantly altering immune system activity. It can be assumed that one of the mechanisms of action on the body of MSCs is to promote the formation of adaptive responses.

scholarly journals The effect of transplantation of bone marrow cells induced by the contact with thymus-derived multipotent stromal cells on the immune system of mice, regenerating after cyclophosphamide treatment

2018 ◽  
Vol 6 (2) ◽  
Author(s):  
D. Demchenko
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Immune System ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Multipotent Stromal Cells ◽  
Hypersensitivity Response ◽  
Cyclophosphamide Treatment ◽  
Lymph Node Cells ◽  
Marrow Cells

The effect of transplantation of syngeneic bone marrow cells (BMCs) after their contact in vitro with thymus-derived multipotent stromal cells (MSCs) for regeneration of damaged by cyclophosphamide immune system of mice was studied.Materials and methods. MSCs were obtained from C57BL/6 mice’s thymus by explants method. BMCs were obtained by flushing the femurs. BMCs were induced for 2 hours on the monolayer of thymus-derived MSCs. The immune deficiency of mice was modelled using cyclophosphamide injection. After that, cell transplantation was performed and the state of the immune system was assessed. The number of erythrocytes, hematocrit, hemoglobin concentration in the peripheral blood; the phases of the cell cycle and apoptosis of mesenteric lymph node cells were determined. The amount of antibody-producing cells in the spleen and the delayed hypersensitivity response was determined. The study of proliferative and cytotoxic activity of natural killer lymphocytes, the analysis of phagocytosis, spontaneous and induced bactericidal activity of peritoneal macrophages were performed.Results. It was shown that unlike intact bone marrow cells, BMCs induced by thymus-derived MSCs provided increased spontaneous proliferative activity of lymphocytes with a decrease in the number of lymph node cells in G0/G1 phase by 6.2 % and an increase the number of lymphocytes in S+G2/M phase by 28 % in comparison with the group of mice treated with cyclophosphamide, as well as the recovery of cellularity of the bone marrow, lymph nodes and spleen. At the same time in the lymph nodes, the number of cells in the apoptosis increased. BMCs induced by MSCs showed a pronounced negative effect on natural cytotoxicity, reducing its rates by 3 times compared with the group of cyclophosphamide-treated mice, and on adaptive immunity: the rates of delayed hypersensitivity response decreased by 1.7 times, number of antibody-producing cells by 1.8 times. Red blood cell regeneration was stimulated by intact BMCs, which was manifested by the normalization of hematocrit and hemoglobin and an increase in the number of reticulocytes in the blood by 2.2 times compared with the group of mice treated with cyclophosphamide.Conclusion. Transplanted BMCs improve erythropoiesis in mice after cyclophosphamide treatment, and BMCs, previously induced by thymus-derived MSCs, lose this ability. BMCs after co-culture are strongly activated to impact on the immune system, which is most likely due to the effect of contact interaction with thymus-derived MSCs, which is known, effectively affect hematopoietic cells and possess immunomodulatory properties.

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Promotes Migration of Human Bone Marrow Multipotent Stromal Cells

Stem Cells ◽  
2008 ◽  
Vol 26 (11) ◽  
pp. 2955-2963 ◽  
Author(s):  
Paola Secchiero ◽  
Elisabetta Melloni ◽  
Federica Corallini ◽  
Antonio Paolo Beltrami ◽  
Francesco Alviano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Stromal Cells ◽  
Tumor Necrosis ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Multipotent Stromal Cells ◽  
Necrosis Factor
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