Search

THz radiation induces a variety of processes in cells and has attracted the attention of researchers in recent decades. Here, data on the effects of high-intensity terahertz (THz) radiation on human directly reprogrammed neural progenitor cells (drNPCs) and on neuroblastoma cells (SK-N-BE (2)) were obtained for the first time. The results demonstrated that the exposure of non-tumor and tumor cells to broadband (0.1-3 THz) THz pulses with the intensity of 21 GW/cm 2 and the electric field strength of 2.8 MV/cm for 30 min induced neither a noticeable genotoxic effect nor a statistically significant change in the proliferative activity and cell differentiation. It was also shown that the combined effect of THz radiation and salinomycin, a promising antitumor agent, on neuroblastoma cells did not enhance the genotoxic effect of this antibiotic. However, further studies involving chemotherapy drugs and other exposure parameters are warranted to introduce this new concept into anti-tumor clinical practice and to enhance the efficacy of the existing approaches.

Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 10 8  cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 10 9 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6-minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo. FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high-resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression., (© The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Objective: In vitro, transglutaminase-2 (TG2)-mediated activation of the β-catenin signaling pathway is central in warfarin-induced calcification, warranting inquiry into the importance of this signaling axis as a target for preventive therapy of vascular calcification in vivo., Methods and Results: The adverse effects of warfarin-induced elastocalcinosis in a rat model include calcification of the aortic media, loss of the cellular component in the vessel wall, and isolated systolic hypertension, associated with accumulation and activation of TG2 and activation of β-catenin signaling. These effects of warfarin can be completely reversed by intraperitoneal administration of the TG2-specific inhibitor KCC-009 or dietary supplementation with the bioflavonoid quercetin, known to inhibit β-catenin signaling. Our study also uncovers a previously uncharacterized ability of quercetin to inhibit TG2. Quercetin reversed the warfarin-induced increase in systolic pressure, underlying the functional consequence of this treatment. Molecular analysis shows that quercetin diet stabilizes the phenotype of smooth muscle and prevents its transformation into osteoblastic cells., Conclusions: Inhibition of the TG2/β-catenin signaling axis seems to prevent warfarin-induced elastocalcinosis and to control isolated systolic hypertension.

Stem cells provide an alternative curative intervention for the infarcted heart by compensating for the cardiomyocyte loss subsequent to myocardial injury. The presence of resident stem and progenitor cell populations in the heart, and nuclear reprogramming of somatic cells with genetic induction of pluripotency markers are the emerging new developments in stem cell-based regenerative medicine. However, until safety and feasibility of these cells are established by extensive experimentation in in vitro and in vivo experimental models, skeletal muscle-derived myoblasts, and bone marrow cells remain the most well-studied donor cell types for myocardial regeneration and repair. This article provides a critical review of skeletal myoblasts as donor cells for transplantation in the light of published experimental and clinical data, and indepth discussion of the advantages and disadvantages of skeletal myoblast-based therapeutic intervention for augmentation of myocardial function in the infarcted heart. Furthermore, strategies to overcome the problems of arrhythmogenicity and failure of the transplanted skeletal myoblasts to integrate with the host cardiomyocytes are discussed.

Donor-recipient cell interactions are essential for functional engraftment after nonautologous cell transplantation. During this process, transplant engraftment is characterized and defined by interactions between transplanted cells with local and recruited inflammatory cells. The outcome of these interactions determines donor cell fate. Here, we provide evidence that lineage-committed embryonic stem cell (ESC)-derived vascular progenitor cells are the target of major histocompatibility complex (MHC) class I-dependent, natural killer (NK) cell-mediated elimination in vitro and in vivo. Treatment with interferon γ was found to significantly upregulate MHC class I expression on ESC-derived vascular progenitor cells, rendering them less susceptible to syngeneic NK cell-mediated killing in vitro and enhancing their survival and differentiation potential in vivo. Furthermore, in vivo ablation of NK cells led to enhanced progenitor cell survival after transplantation into a syngeneic murine ischemic hindlimb model, providing additional evidence that NK cells mediate ESC-derived progenitor cell transplant rejection. These data highlight the importance of recipient immune-donor cell interactions, and indicate a functional role for MHC-I antigen expression during successful ESC-derived syngeneic transplant engraftment.

Recruitment and retention of circulating progenitor cells at the site of injured or ischemic tissues facilitates adult neo-vascularization. We hypothesized that cell therapy could modulate local neo-vascularization through the vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1) axis and by paracrine effects on local endothelial cells. We isolated from rat bone marrow a subset of multipotent adult progenitor cell-derived progenitor cells (MDPC). In vitro, MDPCs secreted multiple cytokines related to inflammation and angiogenesis, including monocyte chemotactic protein-1, SDF-1, basic fibroblast growth factor, and VEGF, and expressed the chemokine receptors CXCR4 and VEGFR1. To investigate in vivo properties, we transplanted MDPCs into the ischemic hind limbs of rats. Elevated levels of the chemokine SDF-1 and colocalization of CD11b(+) cells marked the initial phase of tissue remodeling after cell transplantation. Prolonged engraftment was observed in the adventitial-medial border region of arterioles of ischemic muscles. However, engrafted cells did not differentiate into endothelial or smooth muscle cells. Limb perfusion normalized 4 weeks after cell injection. Inhibition of SDF-1 reduced the engraftment of transplanted cells and decreased endothelial cell proliferation. These findings suggest a two-stage model whereby transplanted MDPCs modulate wound repair through recruitment of inflammatory cells to ischemic tissue. This is an important potential mechanism for cell transplantation, in addition to the direct modulation of local vascular cells through paracrine mechanisms.

Phytosterols are plant sterols found in foods such as oils, nuts and vegetables. Phytosterols, in the same way as cholesterol, contain a double bond and are susceptible to oxidation. The objective of the present study was to assess the potential toxic effects of beta-sitosterol oxides on U937 cells. The effects of increasing concentrations (0-120 microm) of beta-sitosterol oxides on cellular cytotoxicity, apoptosis, antioxidant status and genotoxicity was assessed over 12, 24 and 48 h exposure periods. Following 12 h, the viability of cells treated with 120 microm-beta-sitosterol oxides was reduced to 51.7 % relative to control. At 24 and 48 h, both 60 and 120 microm-beta-sitosterol oxides caused a significant decrease in cell viability. For comparison, a decrease in viability of cells treated with a cholesterol oxide, 7beta-hydroxycholesterol (7beta-OH, 30 microm), was evident at 24 h. An increase in apoptotic cells, assessed using Hoechst 33342, indicates that the mode of cell death in U937 cells following exposure to 7beta-OH (30 microm) and beta-sitosterol oxides (60 and 120 microm) was by apoptosis. The increase in apoptotic cells after 12 h following treatment with 120 microm-beta-sitosterol oxides was accompanied by a decrease in cellular glutathione. Similarly, 7beta-OH (30 microm) treatment resulted in decreased glutathione at 12 h. Catalase activity was not affected by any of the treatments. beta-Sitosterol oxides had no genotoxic effects on U937 and V79 cells as assessed by the comet and sister chromatid exchange assays respectively. In general, the results indicate that thermally oxidised derivatives of beta-sitosterol demonstrate similar biological effects as 7beta-OH in U937 cells, but at higher concentrations.