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 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 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 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 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.

scholarly journals Primarily VEGF-Driven Etiopathogenesis of Tafro Syndrome and Fibroblastic Reticular Cells As a Probable Castleman Cell - Qualitative Metasynthesis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Hannah Lee ◽  
Yurhee Lee ◽  
Amanda Lo ◽  
Leland Powell ◽  
Bhaumik Shah
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Phase 1 ◽  
Germinal Centers ◽  
Marrow Stromal Cells ◽  
Tafro Syndrome ◽  
Stimulation Of

Introduction: Idiopathic multicentric Castleman disease (iMCD) is a heterogenous group of lymphoproliferative disorders believed to be driven by IL-6 with the cell(s) of origin not yet identified (Fajgenbaum et al. 2019). One clinical subtype with thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) is especially aggressive. We encountered a case of TAFRO syndrome that prompted a systematic literature review focusing on the role of VEGF in the pathogenesis of TAFRO syndrome. Interim findings support a role of VEGF in the etiopathogenesis of TAFRO syndrome, with fibroblastic reticular cells (FRCs) as the pathological cell. Methodology: We started with a focused review (step 1, Table 1), followed by empirical review (step 2, Table 1) of published articles on TAFRO syndrome, using methods of qualitative review (Campbell et al. 2011, Levitt 2018) and discussed interim results from phase 1 review (Table 2). The process of reciprocally translating the findings from each study into those from all the other studies in the synthesis, if applied rigorously, provides a method for combining qualitative data in a structured manner. Interim Results: During phase 1 step 1, we reviewed 97 articles published between 2012 and 2020. Majority were case reports. The interim data comprised a total of 34 male and 32 female patients with age ranging from 3 to 85 (median age of 50.5). 26 patients were identified as severe disease and 25 were non-severe per iMCD diagnostic criteria. At the time of presentation, VEGF levels ranged from 44-7520 pg/ml (median 360), IL-6 ranged from 5-4800 pg/ml (median 39.3), and sIL-2Rα ranged from 448-8944 (median 1250). Histologically, hyaline vascular subtype was most common as seen in 24 lymph nodes compared to 4 plasmacytic and 14 mixed. Most common bone marrow cellularity was hypercellular in 19 cases, compared to 16 normocellular, and 4 hypocellular (Table 2). During phase 1 step 2, we explored the fundamental relationship between IL-6 and VEGF. In the lymph node, IL-6 is secreted from endothelial cells and FRCs. IL-6 is further augmented due to stimulation of bone marrow stromal cells by VEGF secreted from FRCs (Tanaka, Narazaki, and Kishimoto 2014). FRCs are the principal cells facilitating entry of dendritic cells and present a cognate antigen by mediating interaction between dendritic cells and T-cells (Fletcher, Acton, and Knoblich 2015, Brown and Turley 2015). Persistent antigenic stimulation leads to the release of VEGF by FRCs in the lymph node and its potentiation through release of IL-6 through VEGF-mediated stimulation of bone marrow stromal cells (Novotny et al. 2008). This reciprocal stimulation between lymph nodes and bone marrow mediate growth effects driven by VEGF, while autocrine-paracrine stimulation of VEGF and IL-6 within lymph nodes and bone marrow drives IL-6 induced flares. Discussion: IL-6 is considered a main driver of pathogenesis underlying TAFRO syndrome, but in the only randomized controlled trial of IL-6 blockade in iMCD, 66% patients did not respond to therapy. IL-6 blockade targets PI3K/Akt/mTOR signaling, an underlying pathway for the pathogenesis of TAFRO syndrome. Our empirical review of literature into TAFRO syndrome reveals elevated VEGF and CD8+ T cells as the hallmarks of TAFRO flares. FRCs are the principal VEGF mRNA-expressing cells in lymph nodes and also contribute to IL-6 production. Bone marrow stromal cells are the principal cells that drive IL-6 release due to potent stimulation from VEGF. This intertwined loop of IL-6 and VEGF becomes a vicious cycle due to chronic antigenic persistence from infections to inflammations. The data from Phase 1 review provide evidence to explain the clinical and pathologic findings in TAFRO syndrome. Atretic germinal centers, characteristic of MCD, result from the mass recruitment of centroblasts and their differentiation into plasmablasts due to chronic VEGF stimulation. IL-6 promotes differentiation of plasmablasts into plasma cells as well as maintaining their survival. We hypothesize that hyperplastic germinal centers and plasmacytosis of plasmacytic lymph node reflect predominant pathologic features during early stages of pathogenesis, while regressed germinal centers and prominent FDCs due to hyalinization of the hypervascular lymph node represent advanced pathologic features. Our findings could potentially be translated into distinguishing clinical stages of MCD. Disclosures No relevant conflicts of interest to declare.

Isolation of Multipotent Stromal Cells from Mouse Bone Marrow

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (4) ◽  
Author(s):  
Aurélie Tormo ◽  
Moutih Rafei ◽  
Jean-François Gauchat
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Mouse Bone Marrow ◽  
Multipotent Stromal Cells

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 68
Author(s):  
Fulvio Massaro ◽  
Florent Corrillon ◽  
Basile Stamatopoulos ◽  
Nathalie Meuleman ◽  
Laurence Lagneaux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Communication ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Major Player

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

Sign in / Sign up

Export Citation Format

Share Document