ABSTRACT
Experiments on F1(CBA×C57BL/6) mice with experimental metastatic melanoma B16 F10 showed that single intravenous injection of xenogeneic bone marrow mesenchymal stromal cells (BM-MSC) in a dose of 106 cells/mouse significantly increased 100-day survival rate of tumor-bearing animals. In contrast, administration of BM-MSC in a dose of 2×106 cells/ mouse reduced survival rates in comparison with the biocontrol (injection of B16 cells alone, 5×105 cells/mouse). This phenomenon can be related to in vivo participation of BM-MSC in reprogramming of resident tissue macrophages, including tumor microenvironment, towards pro- (M1) or anti-inflammatory (M2) phenotype. This is indirectly confirmed by the data on switching from activation to inhibition of ROS-producing activity of blood mononuclears and peritoneal macrophages in tumor-bearing mice in the test of luminol-dependent zymosaninduced chemiluminescence.
Subject(s)
Lung Neoplasms/therapy , Macrophages/immunology , Melanoma, Experimental/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Skin Neoplasms/therapy , Administration, Intravenous , Animals , Cell Count , Cellular Reprogramming/genetics , Cellular Reprogramming/immunology , Female , Humans , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Macrophages/pathology , Male , Melanoma, Experimental/immunology , Melanoma, Experimental/mortality , Melanoma, Experimental/secondary , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Reactive Oxygen Species/immunology , Reactive Oxygen Species/metabolism , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Analysis , Transplantation, Heterologous , Tumor Microenvironment/genetics , Tumor Microenvironment/immunologyABSTRACT
In vivo modifying effects of bone marrow mesenchymal stromal cells of humans and laboratory mice on ROS production by mouse blood mononuclears are studied by luminol-dependent zymosan-induced chemiluminescence after syngeneic and xenogeneic transplantation into systemic blood flow. The chemiluminescent activity of mouse blood mononuclears has increased early (1 day) after syngeneic (mouse mesenchymal stromal cells) and xenogeneic (human mesenchymal stromal cells) transplantation. Later, 7-21 days after syngeneic and xenogeneic transplantation, the chemiluminescent activity of mouse mononuclears is suppressed. The probable mechanisms of involvement of the transplanted mesenchymal stromal cells in reprogramming of the blood mononuclear phagocytes from proinflammatory (M1) to anti-inflammatory (M2) phenotype under conditions of their in vivo interactions are discussed; a frequent manifestation of this reprogramming is transition of the phase of activation into inhibition of ROS-producing activity of macrophages.
Subject(s)
Leukocytes, Mononuclear/metabolism , Mesenchymal Stem Cell Transplantation , Reactive Oxygen Species/metabolism , Animals , Cells, Cultured , Humans , Macrophages/physiology , Mesenchymal Stem Cells/physiology , Mice , Transplantation, Heterologous , Transplantation, HomologousABSTRACT
We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.
