RESUMEN
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.
Asunto(s)
Insuficiencia Cardíaca/terapia , Leucocitos Mononucleares/inmunología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/inmunología , Especies Reactivas de Oxígeno/inmunología , Dinoprostona/inmunología , Dinoprostona/metabolismo , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/patología , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-1alfa/genética , Interleucina-1alfa/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Lipopolisacáridos/farmacología , Linfotoxina-alfa/genética , Linfotoxina-alfa/inmunología , Células Madre Mesenquimatosas/citología , Cultivo Primario de Células , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Trasplante Autólogo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
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.
Asunto(s)
Leucocitos Mononucleares/metabolismo , Trasplante de Células Madre Mesenquimatosas , Especies Reactivas de Oxígeno/metabolismo , Animales , Células Cultivadas , Humanos , Macrófagos/fisiología , Células Madre Mesenquimatosas/fisiología , Ratones , Trasplante Heterólogo , Trasplante HomólogoRESUMEN
We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.
Asunto(s)
Lesiones Encefálicas/terapia , Células Madre Mesenquimatosas/citología , Neuronas/citología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
The study undertaken 3 years ago examined the effect of systemic transplantation of autologous mesenchymal stem cells (MSC) in the complex therapy of 27 patients with pulmonary tuberculosis, including 15 patients with multidrug-resistant pulmonary tuberculosis and 12 with extensive drug resistance of Mycobacterium tuberculosis. All the patients were bacteria-discharging persons with disseminated destructive processes in lung tissue, most (n=17) of them had chronic fibrocavernous tuberculosis. In all the patients, previous long specific antituberculous treatment was ineffective or inadequately effective. After systemic MSC transplantation, 16 patients were followed up for 1.5-2 years or more and the remaining 11 patients for at least 6 months. After MSC administration, a positive clinical effect was observed in all 27 cases; bacterial discharge stopped in 20 patients after 3-4 months; resolution of sustained lung tissue cavities further occurred in 11 patients. At present, a persistent remission of a tuberculous process may be stated in 9 of the 16 patients in whom MSCs were transplanted 1.5-2 years, significant positive bacteriological and morphological changes are observed in 6 patients. Thus, inclusion of transplantation of the autologous MSCs propagated in the culture into a course of antituberculous therapy may be a promising procedure for enhancing the efficiency of therapy in patients with resistant forms of pulmonary tuberculosis.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Tuberculosis Resistente a Múltiples Medicamentos/cirugía , Tuberculosis Pulmonar/cirugía , Adulto , Estudios de Seguimiento , Humanos , Radiografía Torácica , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico por imagen , Adulto JovenRESUMEN
The effects of whole-body gamma-irradiation in different doses on the distribution of (188)Re-labeled mesenchymal stem cells obtained by culturing of the rat bone marrow cells were studied in different organs and tissues of animals after intravenous (systemic) injection. Irradiation stimulated homing of (188)Re-labeled mesenchymal stem cells in organs and tissues of animals in comparison with this process in intact non-irradiated rats. The intensity of homing increased with increasing the irradiation dose and decreased with prolongation of the period between irradiation and systemic transplantation. It was hypothesized that increased migration of transplanted mesenchymal stem cells into irradiated organs and tissues can be caused by developing cell death processes. It seems that systemic transplantation of mesenchymal stem cells shortly after irradiation can be used for stimulation of reparative processes in damaged tissues.
Asunto(s)
Radioisótopos de Cobalto/administración & dosificación , Rayos gamma , Trasplante de Células Madre Mesenquimatosas/métodos , Radioisótopos/farmacocinética , Renio/farmacocinética , Irradiación Corporal Total/métodos , Animales , Células Cultivadas , Radioisótopos de Cobalto/farmacología , Inyecciones Intravenosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Dosis de Radiación , Radioisótopos/administración & dosificación , Ratas , Ratas Wistar , Renio/administración & dosificación , Factores de Tiempo , Distribución Tisular/efectos de la radiación , Trasplante AutólogoRESUMEN
In vitro chemiluminescent test showed that human bone marrow mesenchymal stem cells and conditioned media dose-dependently inhibit production of reactive oxygen species by macrophages: 50% inhibition of chemiluminescence (compared to biocontrol) was observed at 1:1 mesenchymal stem cell/macrophage ratio or after addition of 20-25% conditioned media to the incubation medium. The observed mechanism of inhibition of production of reactive oxygen forms can play an essential role in the formation of local immunosuppressive microenvironment in the organism after allogenic transplantation of mesenchymal stem cells.