[Transplantation of mesenchymal stem cells in multiple sclerosis].

To assess safety and tolerability of treatment with autologic multipotent mesenchymal stem cells (MSC) in multiple sclerosis (MS), we have obtained autologic red bone marrow-derived MSC from 8 patients. Proliferation, immunophenotype and caryotype of MSC, their sterility, the absence of hemopoetic cells, chromosomal aberrations and signs of aging were controlled during the cell growth. The inverse injection of MSC in patient's blood was conducted in accordance to the elaborated protocol in a short intravenous infusion in dose 2.0 x 10(6)/kg of body mass once in 30 days. The duration of treatment was from 4 to 8 months. The efficacy of treatment was assessed after 4, 8 and 12 months. All patients tolerated repeated intravenous infusions of autologic MSC well with no significant side-effects as in the early as well in the remote periods of treatment. The distinct positive effect was seen in some cases 2 months after the beginning of treatment. The improvement of 0.5 point on EDSS was seen in 5/8 patients after 4 months. After 12 months, the improvement of 0.5-1 point on EDSS was seen in 6/8, stabilization in 1/8, progression in 1/8. These results revealed the safety of the elaborated protocol of treatment and the moderate clinical efficacy of treatment in non-curable patients or those with poor response to treatment that suggested continuing the study and enrollment of new patients.

[Murine embryonic stem cells as a model object for human embryonic stem cells research].

During several last decades mouse embryonic stem cell (mESC) were used as a model object for the research of human embryonic stem cells (hESC). The validity of such approach is still not finally proved. At the same time there is a large amount of literary data available, which gives evidences of many substantial differences between these two cell types. The analysis of the literature has shown that there are differences concerning the regulation of proliferation, self-renewal maintenance, and the regulation of differentiation of ESC. Thus, mESC can be considered as a model object for hESC studies only in some aspects of their biology. The alternative model objects, such as primate ESC, are also briefly discussed in this review.

[Stem cells from adult differentiated tissues].

The review thoroughly describes all types of adult stem cells which have been isolated by the present time - hematopoietic, muscle, neural, skin, endothelial, intestinal and mesenchymal stem cells. Their isolation, in vitro cultivation, and possible application in cell therapy of various diseases are discussed. Mesenchymal stem cells (MSC) are of great concern now because they are, in the authors' opinion, the most promising material for application in the therapy of humans.

[Cell therapy for myocardial infarction].

The review discusses cell therapy; one of the most promising approaches to myocardial infarction treatment. The possibility to use cell material of various origins is analyzed. The review sums up data on the application of fetal and neonatal cardiomyocytes, myoblasts, bone marrow mononuclear fraction, hematopoietic and mesenchymal stem cells (MSX) as cell therapy agents. The conclusion is made that MSC are promising cell material for myocardial infarction therapy. MSC are able to migrate to the injured area, differentiate into myocardial lineage. They produce a wide range of factors that stimulate angiogenesis and increase viability of cells, including cardiomyocytes.

[Mesenchymal stem cells-based therapy of brain ischemic stroke in rat].

Mesenchymal stem cells (MSCs)-based therapy is a promising modern attempt to improve the recovery after stroke. Experiments were carried out on inbred Wistar-Kyoto rats. MSCs were isolated, expanded in cultute and labeled with vital fluorescent dye PKH-26. Animals were subjected to middle cerebral artery occlusion (MCAO), followed by injection of 5 x 10(6) rat MSCs into the tail vein 3 days after MCAO. Control group animals received PBS injection (negative control). Therapy results were estimated by the following parameters: behavioral and neurological testing, the brain injure area, the state of damaged region "border" zone and the vessels quantity in the "borden" area. It was shown that control group animals (PBS injection) did not restore their initial behavioral and neurological state, while the experimental group animals (MSCs injection) showed the same parameters as intact rats at 2-3 weeks after MCAO. The size of the damaged region in the control group was approximately 1.5 as large as in the experimental group. The damage in the experimental group was limited to neocortex; caudate nucleus, capsula externa and piriform cortex remained uninjured. Small vessels quantity in the "border" regions was twine higher compared to control group and was approximately equal to an intact brain vessel number. Moreover, it was shown for the first time that after MSCs transplantation the vessels quantity in the neocortex and caudate putamen of contralateral hemisphere was twice as much as in control. We demonstrated that the MSCs transplantation definitely exerted a positive influence upon the brain tissue reparation after stroke.

[Mesenchymal stem cells transplantation influences upon dynamics of morphological changes in rat brain after stroke].

Study of dynamic morphological changes if the brain after ischemic stroke is an important phase of pre-clinical trial of mesenchymal stem cell (MSC) therapy for this widespread disease. Experoments were carried out in inbred Wistar-Kyoto rats. MSCs were isolated, expanded in culture and labeled with vital fluorescent dye PKH26. Animals were subjected to middle cerebral artery occlusion (MCAO) followed by injection of 5 x 10(6) rat MSCs into the tail vein on the day of MCAO. Control group of animals received PBS injection (negative control). Animals were sacrificed in 1, 2, 3 and 5 days and in 1, 2, 4 and 6 weeks after operation. MSCs were revealed in the brain on the third day transplantation. They distributed around brain vessels in both the ipsilateral and contralateral hemispheres. This pattern of distribution remained unchanged during 6 weeks of observation. It was demonstrated that inflammation process and scar formation in the experimental group progressed 25-30 % faster than in the control group. MSC transplantation stimulated endogenous stem cell proliferation on the subependimal zone of lateral ventricles (subventrecular zone). What is more, MSC injection showed neuroprotective effect: almost all penumbra neurons in animals treated with cell therapy retained their normal structure, whereas in animals of control group penumbra neurons died or had signs of serious damage.

[The influence of mesenchymal stem cell transplantation time on myocardial reparation in rat experimental heart failure].

Mesenchymal stem cells (MSCs) have an ability to migrate in the organism to injured tissue to exert influence on inflammation and reparation in these regions. The aim of this study was to determine the optimal time of MSCs transplantation for myocardial reparation in rat experimental heart failure. The experiments were carried out on inbred line Wistar-Kyoto rats. Myocardial experimental infarction (EI) was induced by ligation of the left descending coronary artery. MSCs were isolated from bone marrow, cultivated in vitro and injected into the tail vein on the day of experimental infarction operation. It was shown that the time of MSCs transplantation exerted an essential influence on angiogenesis in a damaged myocardium, on ventricular dilatation and morphological structure of the scar. The best time for MSCs transplantation was determined within two days before EI, and seven days after EI. As a result, the overload of the border zone of infarct region decreased, and no features of infarction relapse were shown in the border zone.

[The influence of mesenchymal stem cells on bone tissue regeneration upon implantation of demineralized bone matrix].

Mesenchymal stem cells (MSC) are resident pluripotent cells of bone marrow stroma. MSC are able to differentiate into chondroblasts, adipocytes, neurons, glia, cardiomyocytes, or osteoblasts. The problem of MSC usage in cell therapy of bone defects is widely discussed at present. The experiments were carried out using rats of inbred line Wistar-Kyoto. MSC were isolated from bone marrow and cultivated in vitro. Demineralized bone matrices (DBM) were obtained from parietal bones of rats and hens. Part of DBM was loaded with MSC. Bone defects were made in cranium parietal regions. DBM with or without MSC or metal plates were transplanted in these regions. It was shown that the application of MSC increased angiogenesis and osteogenesis in the damaged bone. The implantation of rat's DBM with MSC led to the formation of a full value bone. MSC suppressed inflammation, when transplantation of hen's DBM was carried out. The application of MSC always improved bone tissue regeneration.

[Mesenchymal stem cell transplantation for myocardial reparation of rat experimental heart failure]. / Terapiia éksterimental'nogo infarkta miokarda u krys s pomoshch'iu transplantatsii singennykh mezenkhimnykh stvolovykh kletok.

Mesenchymal stem cells (MSC) are resident pluripotent cells of bone marrow stroma. MSC have the ability to differentiate into osteoblasts, chondroblasts and adipocytes, neurons, glia and also into cardiomyocytes. The problem of MSC use in cell therapy of various diseases and in myocardial infarction therapy is widely discussed at present. The experiments were carried out on the inbred line Wistar--Kyoto rats. Myocardial experimental infarction (EI) was induced by left descending coronary artery ligation. MSC were isolated from bone marrow, cultivated in vitro and injected into the tail vein on the day of experimental infarction operation. It was shown that the structure of injured myocardium in experimental group significantly differed from that in control group. MSC transplantation led to inflammatory process acceleration and to increased angiogenesis in the damaged myocardium; also, live cardiomyocyte layers were detected in the scar. As a result, ventricular dilatation and overload of the border zone of infarct region decreased, no features of infarction relapse were shown in the border zone.