The specific features of the formation of metal nanoparticles under X-ray radiation in interpolyelectrolyte complex (IPEC) films based on polyacrylic acid and polyethyleneimine with different silver ion content were studied. IPEC films were irradiated in aqueous-alcoholic medium. Electron microscopy demonstrated that the formation of silver nanoparticles occurred in zones regularly located by film thickness. It was found that nanoparticle size and spatial distribution in IPEC films depended on the initial concentration of silver ions within the sample and on the absorbed dose of radiation. The obtained film nanocomposites are promising objects for application as antibacterial and catalytic materials.

The radiational chemical production of silver nanoparticles offers promising prospects for the synthesis of the antibacterial materials in the matrix of the nontoxic poly(vinyltriazole). Use of the optical spectroscopy for the electronic transmission microscopy shows that nanoparticles of the average size of 4 nm are formed in the radiated suspensions of poly(1-vinyl-1,2,4-triazole). The analysis of the data of the optical spectroscopy reveals that nanoparticles are formed in several stages. At the first stage, the formation of clusters is prevalent and the second stage provides the assembly of nanoparticles through the reduction of silver ions on the surface of the clusters.

The effect of preliminary annealing of semicrsytalline high-density polyethylene films on the parameters of nanoporous structure formed during deformation of polymers in physically active liquid environments via the intercrystallite crazing has been studied. Optimal conditions providing the development of a stable open-cell polymeric materials with a high level of porosity (50%) and pore size below 10 nm have been elavorated. For the first time, the in situ reduction of copper ions into copper(0) in the pores of the highdensity polyethylene nanoporous polymer matrix has been carried out using the radiation-chemical reduction method. The reaction has led to the formation of nanoscale copper particles within the polymer, which makes it possible to produce metal-polymer nanocomposites with valuable functional properties.

In murine bone-marrow stromal microenvironment cells and in human multipotent mesenchymal stromal cells (MMSCs), proinflammatory cytokine interleukin-1 beta (IL-1β) serves as a growth factor. In murine bone tissue, IL-1β expression increases in vivo after irradiation. Here, we have presented our evaluation of the effects of exogenous IL-1β on the expression of NF-kB transcription factors in human MMSCs and stromal layer cells of murine long-term bone marrow cultures (LTBMCs). The cytokine signaling pathway was also activated in murine LTBMC by braking electron radiation in doses of 3–12 Gy. The level of expression of genes that code for IL-1β, IL-1β type-I receptor and NF-kB and IKK protein families have been studied at different time points post exposure. In both human and murine stromal cells, exogenous IL-1β led to an increase in the level of expression of its own gene, while levels of expression of NF-kB and IKK gene families were not substantially changed. Nevertheless, in human cells, a significant correlation between levels of expression of IL-1β and all NF-kB family genes was detected. It points to a similarity in IL-1β signal pathways in mesenchymal and hematopoietic cells, where the posttranslational modifications of NF-kB transcription factors play a major role. The irradiation of murine LTBMC resulted in a transient increase in the expression of genes that code NF-kB transcription factors and IL-1β. These results indicate an important role of Rel, Rela, Relb, and Nfkb2 genes in the induction of IL-1β signal pathway in murine stromal cells. An increase in IL-1β expression after the irradiation of stromal cells may be related to both the induction of inflammation due to massive cell death and to a profound stimulation of the expression of this proinflammatory cytokine expression.

BACKGROUND:Multipotent mesenchymal stromal cells (MSCs) are used for prophylaxis of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Not all samples of MSC are efficient for aGvHD prevention. The suitability of MSCs for aGvHD prophylaxis was studied.METHODS:MSCs were derived from the bone marrow (BM) of HCT donor and cultivated for no more than three passages. The characteristics of donor BM samples including colony-forming unit fibroblast (CFU-F) concentration, growth parameters of MSCs, and the relative expression levels (REL) of different genes were analyzed. MSCs were injected intravenously precisely at the moment of blood cell reconstitution.RESULTS:MSCs infusion induced a significant threefold decrease in aGvHD development and improved overall survival compared with the standard prophylaxis group. In ineffective MSC samples (9.4%), a significant decrease in total cell production and the REL of CSF1, FGFR1, and PDGFRB was observed. In all studied BM samples, the cumulative MSC production and CFU-F concentrations decreased with age. The expression levels of FGFR2, PPARG, and VEGF differed by age.CONCLUSIONS:A universal single indicator for the prediction of MSC eligibility for aGvHD prophylaxis was not identified. A multiparameter mathematical model for selecting MSC samples effective for the prevention of aGvHD was proposed.

irradiated interpolyelectrolyte complexes D.I.Klimov,* A.A.Zezin, S.S.Abramchuk, E.A.Zezina, M.Yang 1Enikolopov Institute of Synthetic Polymeric Materials, a foundation of Russian Academy of Sciences, Profsoyuznaya ul. 70, Moscow, 117393 Russia 2Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991 Russia 3Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China

Allogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, the foremost being graft-versus-host disease (GVHD). Due to the lack of efficiency of the existing methods of GVHD prophylaxis, new methods are being actively explored, including the use of donors’ multipotent mesenchymal stromal cells (MMSC). In this work, we analyzed the results of acute GVHD (aGVHD) prophylaxis by means of MMSC injections after allo-BMT in patients with hematological malignancies. The study included 77 patients. They were randomized into two groups — those receiving standard prophylaxis of aGVHD and those who were additionally infused with MMSC derived from the bone marrow of hematopoietic stem cell donors. We found that the infusion of MMSC halves the incidence of aGVHD and increases the overall survival of patients. Four of 39 MMSC samples were ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index) and the MMSC properties of these donors (growth parameters, level of expression of 30 genes involved in proliferation, differentiation, and immunomodulation) revealed no significant difference between the MMSC that were effective or ineffective for preventing aGVHD. We used multiple logistic regression to establish a combination of features that characterize the most suitable MMSC samples for the prevention of aGVHD. A model predicting MMSC sample success for aGVHD prophylaxis was constructed. Significant model parameters were increased relative expression of the FGFR1 gene in combination with reduced expression levels of the PPARG and IGF1 genes. Depending on the chosen margin for probability of successful application of MMSC, this model correctly predicts the outcome of the use of MMSC in 82–94% of cases. The proposed model of prospective evaluation of the effectiveness of MMSC samples will enable prevention of the development of aGVHD in the maximal number of patients.

Multipotent mesenchymal stromal cells (MMSCs) have been demonstrated to produce mature stromal cells and maintain hematopoietic progenitor cells (HPC). It was previously demonstrated that interleukin-1 beta (IL-1 beta) stimulates the growth of the stromal microenvironment in vivo. The aim of this study was to investigate the effect of IL-1 beta treatment of human MMSCs on their proliferative potential, gene expression, immunomodulating properties, and their ability to support HPCs in vitro. Human bone marrow-derived MMSCs were cultivated in standard conditions or with IL-1 beta. The cumulative cell production was assessed for five passages. After withdrawal of IL-1 beta, MMSC clonal efficiency was investigated, and the maintenance of HPCs on top of MMSCs layers was estimated using cobblestone area forming cell (CAFC) and long-term culture initiating cell (LTC-IC) assays. The effect of untreated MMSCs or MMSCs pretreated with IL-1 beta on lymphocyte proliferation was studied by CFSE staining. The relative expression level of various genes by MMSCs was analyzed using RT-qPCR. The administration of IL-1 beta elevated MMSCs clonal efficiency and total cell production but did not affect lymphocyte proliferation. MMSCs pretreatment with IL-1 beta enhanced their ability to maintain HPCs, as detected by CAFC assay, and it altered the expression levels of genes participating in HPC regulation by stromal cells, e.g., adhesion molecules (ICAM1) and growth factors (SDF1). This study revealed the ability of IL-1 beta to stimulate MMSCs proliferation and enhance their potential to maintain HPCs. MMSCs are considered a stromal niche component in vitro. The combined in vitro and previous in vivo data suggest that IL-1 beta is a systemic regulator of the stromal microenvironment.

The formation of nanoparticles during the radiation-induced chemical reduction of silver ions, copper ions, and nickel ions in films based on poly(acrylic acid)-poly(ethylenimine) complexes are studied via electron microscopy. This approach allows preparation of composites containing nanoparticles that are randomly distributed in the polymer matrix and materials with a regular spatial distribution of nanoparticles across the film thickness and in subsurface layers. The structure of metal-polymer hybrid materials is dependent on the irradiation conditions, the type of reduced metal ions, and their initial content in polymer matrices. The ratio between the rate of nucleation and the rate of growth of nanoparticles in the matrices of interpolyelectrolyte complexes depends on the intensity of the absorbed dose and on the mechanisms of reduction of metal ions and formation of clusters. The IR spectroscopic studies reveal the effect of nanoparticles on the chemical structure of the polymer matrix.

The features of nanoparticle formation by the radiation-chemical reduction of Cu2+ ions in polyacrylic acid-polyethyleneimine complexes have been studied. It has been shown that the swollen film/aqueous alcohol medium interphase exchange of the reducing species and the specifics of X-ray energy transfer play an important role in the formation of metal particles in the subsurface layer of polymer matrixes. An analysis of EPR and X-ray diffraction data shows that an acetaldehyde admixture increases the Cu2+ reduction rate of and enables the growth of nanoparticles.