Possible therapeutic effect of systemic (intravenous) transplantation of autologous mesenchymal stem cells was studied in experiments (C57Bl/6 mice) and pilot clinical trial. Clinical trial was performed on 11 patients with radiation-induced lung injuries developed after combined chemotherapy and radiation therapy for lymphogranulomatosis or breast cancer. The patients were subjected to single transplantation of mesenchymal stem cells and course of standard pharmacotherapy. The method for isolation of autologous mesenchymal stem cells was licensed. The transplantation of mesenchymal stem cells was followed by a decrease in the mortality rate of mice with radiation-induced lung injury. Clinical trial showed that cell therapy with autologous mesenchymal stem cells does not induce progression of the underlying oncological disease. Parameters of spirography, immune status, lung scintigraphy, and markers for inflammation and tissue hypoxia in the patients remained practically unchanged 1 year after the treatment. These clinical signs reflect stabilization of the radiation process.

A complex of reactions regulating the number of cells in organs and tissues under normal and pathologic conditions is one of the most important systems of multicellular organisms. In this system, which controls both cell proliferation and clearance, clearance has been given special attention during the last three decades. Some stages of the clearance are known (the choice of "unwanted" cells, their destruction not affecting the surrounding tissue, and, finally, removal of the corpses), and undeniable progress has been achieved in the understanding of the second stage mechanisms, whereas mechanisms of elimination per se of cells or their fragments still continue to be terra incognita. The clearance of such cells is mainly determined by different components of natural and adaptive immunity: phagocytes, complement, opsonins, antigen-presenting cells, etc. Recently specific "danger signals", such as hydrolases, DNA, heat shock proteins, and other potential immunogens released by cells during their elimination have been discovered. Entering the extracellular space, these signals induce inflammation and injury of the surrounding tissues, i.e., autoimmune reactions. Heat shock proteins, in addition to chaperon activity, act as signaling, costimulating, and antigen-carrying molecules in the interactions of dying cells and the immune system.

Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic, angiogenic, and, presumably, neurotrophic effects. The therapeutic effect visually manifested on day 2 after intravenous injection of mesenchymal stem cells during the early period of reparative regeneration of ischemic cell and tissue structures of the brain. The neuroprotective effect of mesenchymal stem cells was more pronounced against the background of basic therapy.

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.

We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy.