[Effect of mesenchymal stem cells and entero-absorbent on cardiac function in rats following local irradiation of the chest].

Cardiac function in Wistar male rats was assessed by ECG records for 28 days following exposure of the chest to γ-rays at a dose of 6 Gy, dose rate 4 Gy/min. The exposed rats experienced a moderate cardiac ischemia and a certain increase in the load on the atria. The use of clay of Kaluga deposit and mesenchymal stem cells reduced the adverse radiation effects.

[Complete elimination of cytomegalovirus without antiviral therapy after systemic transplantation of mesenchymal bone marrow stromal cells in a patient with ulcerative colitis].

Cytomegalovirus infection (CMV) has become in the last 15-20 years one of the most important problems of scientific research and clinical high attention. This is due to new information discovered about its leading role in the origin, development, and the outcome of a large group of serious diseases. Cytomegalovirus (CMV) is one of the most common causative agents of opportunistic infections (OI) in patients with IBD, which are mandatory feature of the state of immunodeficiency. Numerous studies in vivo and in vitro studies have demonstrated that mesenchymal stromal cells (MSCs) suppress immune reactions to allogeneic stimulation, but not the invasion of infection, as well as themselves possess antiviral and antimicrobial activity, as demonstrated in this clinical case.

[Complete elimination of cytomegalovirus without antiviral therapy after systemic mesenchymal stromal cell transplantation in a patient with ulcerative colitis (a clinical case)].

Cytomegalovirus (CMV) is one of the common pathogens of opportunistic infections in patients with inflammatory bowel diseases. When the patients are treated with immunosuppressants that make them more susceptible to CMV, the course of ulcerative colitis (UC) becomes considerably worse. Antiviral therapy sometimes can reduce the risk of complications and the rate of colectomies. At the same time, antiviral therapy is not mandatory for all UC patients with CMV infection, as shown by the results of numerous investigations. One of the properties of mesenchymal stromal cells (MSC) is to suppress the body's immune reactions to allostimulation, rather than to infection invasion. In vivo and in vitro studies have demonstrated that MSCs have antiviral and antimicrobial activities. The described clinical case shows that clinical improvement occurred and a drastic activation of proliferative processes in the colonic mucosa was detected in the patient with UC after MSC transplantation. Administration of cultured MSCs also promoted the elimination of CMV without antiviral therapy and the overcoming of hormone dependence/ resistance in the patient with UC.

[Where intestinal epithelial stem cells are localized? About molecular markers].

Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008-2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny. 1) Although anatomic localization of intestinal epithelium cells lacking marked morphological and biochemical differentiation markers (the lower third of intestinal and colon crypts) is known for about 40 years results of their experimental identification, isolation and detection of their functional characteristics still represent the subject for discussions. Particularly, it remains unclear, which SC are involved in crypt regeneration: the same as those involved into homeostatic renewal or their various subpopulations or early SC progenies acquired stem features by reprogramming? 2) In addition, most detected biochemical markers of potential SC are common for SC from other tissues of embryonic and mature organisms so it is possible to apply method developed for intestinal epithelium for their isolation. 3) Data on induction of intestinal epithelium polyps and neoplasias by mutations in genes encoding SC markers and identification of biochemical characteristics of potential SC in these tumors support the hypothesis of stem tumor cell origination from normal SC or their earliest progeny. In general, facts considered in this review may be useful for both development of optimal methods for the use of SC in cell therapy (as the source of humoral factors), regenerative medicine (as the source of differentiated cells for restoration of injured tissue), and also for targeted search of antitumor drugs (SC as the target) and preparations modifying genetic and epigenetic reactions of SC to genotoxic and stress treatments.

[Quality of life in inflammatory bowel disease patients].

OBJECTIVE: To study the quality of life (QOL) patients with inflammatory diseases (IBD), gender and age characteristics of QOL, as well as its dynamics under the influence of biological and standard therapy. MATERIAL AND METHODS: Investigation of QOL using the SF-36 was performed on 90 patients with IBD, among them 35 with Crohn's disease, 55--ulcerative colitis. Mean age 35.2 +/- 1.2 years, men--53, women--37. Severity of symptoms of IBD (by Best and Truelove): mild--7 (7.7%), moderate--69 (76.6%), severe--14 (15.7%), extraintestinal manifestations were present in 34 (37.8%) patients. After a year was conducted the survey in 31 patients (group 1) after standard therapy with 5-aminosalicylic acid (5-ASA), corticosteroids (GCS), 29 patients (Group 2)--after systemic transplantation of mesenchymal stromal cells (MSCs) of 27 patients (group 3)--Treatment with infliximab (IFX). The results. QOL was reduced in all patients in all scales of the questionnaire, including adverse changes in the psycho-emotional and social spheres. In the dynamics under the influence of the therapy, especially in achieving complete clinical and endoscopic remission, tendency to improve the performance of most QOL was more pronounced in patients with IBD treated with biological therapy MSCs and inflation, compared with patients receiving standard therapy. Identified gender differences in indicators of QOL that requires to develop psychosocial rehabilitation programs that take into account these differences. It is concluded that the need for participation of psychologists and neuropsychiatrists gastroenterologist in joint management and treatment of IBD. Was concluded the necessity of psychologists and neuropsychiatrists and gastroenterologist participation in joint management and treatment of IBD.

[The immune status changes in patients with inflammatory bowel disease under the influence of mesenchymal stromal cells and infliximab therapy].

Out of 28 patients with inflammatory bowel disease in 11 (39.3%) revealed the presence of autoantibodies to gastric parietal cells. Appointment of MSC and infliximab did not lead to a reduction in antibody levels, in fact, in 6 (21.4%) patients had a further increase in the content of mentioned autoantibodies. Identification of autoantibodies to gastric parietal cells is considered as adherence to IBD autoimmune gastritis (formation of a systemic process) that requires use of corticosteroids. Transplantation of mesenchymal stromal cells in IBD reduces enhanced circulation of autoantibodies against antigens of neutrophils cytoplasmic structures, thereby reducing the severity of autoimmune reactions. Transplantation of MSCs reduces autoaggression in patients with ulcerative colitis, reducing the autoreactive clone of B lymphocytes (CD19+CD5+). Analysis effectiveness of the therapy. Transplantation of MSCs in IBD has a systemic immunoregulatory effect: on the one hand, stimulates oppressed cytokine synthesis, on the other--reduses the intensity of the autoimmune reactions and activity of pathological processes. Infliximab selectively blocks TNF-alpha, without affecting other proinflammatory cytokines.

[Experimental study of the effect of detoxification with enterosorbents on the function of irradiated myocardium].

Increase in intoxication products, such as medium size peptides, indole and myoglobin, in urine was observed in Wistar rats after exposure of their chest to gamma-radiation at a dose of 6 Gy (dose rate 4 Gy/min). The rats exhibited moderate ischemic ECG. Administration of enterosorbents, such as Smekta and Clay of Kaluga deposit, to the irradiated rats resulted in the decrease of the toxicant content in the animals and the recovery of the cardiac function on the 28th day. These sorbents had practically a similar efficacy.

[Transplantation of allogeneic mesenchymal stem cells from the bone marrow increases duration of remission and reduces the risk of ulcerative colitis relapse].

The first results of allogeneic mesenchymal stem cells from the bone marrow transplantation to patients with ulcerative colitis demonstrated improved clinical course. We found an increasing in the duration of remission in patients with chronic recurrent and continuous recurrent course of ulcerative colitis. Also it was noted reducing the risk of relapse, and reducing the frequency of hospital admissions compared with medication therapy with only 5 aminosalicylic acid and glucocorticosteroid.

[Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases].

AIM: to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID). SUBJECTS AND METHODS: Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion. RESULTS: A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only. CONCLUSION: The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

[Age as a prognostic factor in the treatment effectiveness of patients with ulcerative colitis with help of mesenchymal stromal cells].

The aging process decreases the efficiency of the immune system is to maintain the constancy of the antigenic composition of the body. The process of recognition of own and foreign antigens is becoming less accurate, the intensity of immune responses is reduced. This leads to a characteristic of aging immunopathologic syndromes: an immune deficiency, autoimmunity, increased levels of circulating immune complexes, increased cases of benign monoclonal gammopathy. The weakening of the immune processes affected the clinical features of ulcerative colitis in the elderly. In old age, systemic manifestations of disease are observed in 2 times less, and local--in 2 times more likely than patients aged 20-40 years, with local complications such as profuse bleeding and a decrease in the lumen of the colon, there are 3-4 times more often. Thus, age is a factor that determines the characteristics of the course of ulcerative colitis, the severity of extra-systemic manifestations, prognosis and, consequently, response to therapy. Transplantation of mesenchymal stromal cells in elderly patients with ulcerative colitis is less effective than in patients with young and middle age.

[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].

UNLABELLED: The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC). MATERIALS AND METHODS: The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose. RESULTS: In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy. CONCLUSION: The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.

[Stem cells of intestine epithelium. Survival mechanisms and microbiota role].

The thanatogenetic mechanisms of stem cells (SC) of rapidly renewing system of intestinal epithelium still remain unclear. On the one hand, they are definitely involved into basic mechanisms of carcinogenesis in the gastrointestinal tract, because dysregulation of programs responsible for elimination of "unwanted" mutant cells (which are normally under immune and own intrinsic control) is one of the reasons of neoplastic expansion. On the other hand, elucidation and characterization of the regulatory machinery controlling SC survival are interrelated with problems of clinical medicine, including the increase of therapeutic efficiency of treatment of inflammatory and ulcer lesions of the gut, traumatic and surgical wounds, as well as restriction of side effects in normal tissues induced by application of intensive methods chemo- and radiotherapy of cancer. The latter is especially important for treatment of blood diseases and tumors of peritoneal cavity organs mainly due to bone marrow and intestinal epithelium damage. (These tissues are the most sensitive to these treatments.) The review considers data on exogenous and genetic modifiers of SC survival, and also the basic principles of mechanisms involved into renewal and regeneration of SC and the effects of microbiota on these processes.

[Application of allogeneic mesenchymal stem cells in complex patients treatment with ulcerative colitis].

Systemic transplantation of mesenchymal stem cells (MSC) is known to promote reparative process in a number of tissue damage as well as mucous healing one. It provided the basis for our study which was aimed to the effect of systemic transplantation of allogenic MSC (intravenous transfusion) in complex therapy of patients with Ulcerative Colitis.

[Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis].

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.

[Survival/death modifiers of intestine epithelium stem cells and thanatological mechanisms].

Till now the thanatological mechanisms that regulated the proliferation and the clearance of the stem cells (SC) in fast renewal systems of organism--intestinal epithelium remain insufficiently investigated as in haematopoietic system too. The relevance of such researches is supported by an essential role of these mechanisms in pathogenesis of widely widespread inflammatory and hyperproliferative diseases. In particular inhibition/disregulation of elimination for the "undesirable", mutant cells leaving from under immune and own control is one of the reasons for neoplastic cell expansion. In this review were summarized data about some mechanisms determining SC-destruction in animals treated by ionizing radiation or antineoplastic preparations, and also treated by modifiers of SC-radiosensitivity.

[The influence of some retarding agents NOS of dihydrothiazine-thiazoline rank on postradiational of recovery endogenous CFU-S-8 of mice].

In this work the attempt to estimate a nitric oxide (NO*) role in regulation of the number of pool haemopoietic stem cells at the irradiated mice was made. With this purpose the number of new compounds from dihydrothiazine-thiazoline line was synthesized, their NO-inhibiting activity was investigated in vivo by the method of ESR-spectroscopy of spin trap and their influence on an output endogenous spleen colonies (CFU-S-8) after the total sublethal y-irradiation of mice in a doze of 6 Gy was also investigated. Was shown, that the tested compounds reduced the contents of NO* in a liver tissue of mice which have received an injection of nitric oxide synthesis inductor - lipopolysaccharide, and also increased an output CFU-S-8 forming endogenous colonies in the spleen of the irradiated mice. Received data testify to perceptivity of search radioprotective agents among NO* synthesis inhibitors.