Influence of Egr-1 in cardiac tissue-derived mesenchymal stem cells in response to glucose variations

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes in in vitro glucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1-/-). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1 -/- cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1-/- lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1-/- compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications. © 2014 Daniela Bastianelli et al.

Stem cell therapies for ischemic cardiovascular diseases

Myocardial infarction results in loss of cardiac muscle and deficiency in cardiac performance. Likewise, peripheral artery disease can result in critical limb ischemia leading to reduced mobility, non-healing ulcers, gangrene and amputation. Both of these common conditions diminish quality of life and enhance risk of mortality. Successful advances in treatment have led to more people surviving incidences of myocardial infarction or living with peripheral artery disease. However, the current treatments are inadequate in repairing ischemic tissue. Over the last 5 years, a vast number of patents have been submitted concerning the use of stem cells, which correlates with the exponential growth in stem cell publications. Exploiting stem cell therapy offers a real potential in replacing ischemic tissue with functional cells. In this paper, we review recent patents concerning stem cell therapy that have the potential to provide or potentiate novel treatment for ischemic cardiovascular disease. In addition, we evaluate the promise of the inventions by describing some clinical trials that are currently taking place, as well as considering how current research on ischemic cardiovascular disease may change the patent landscape in the future.

Thermal stability of porous sol-gel phosphosilicates and their surface area stabilisation by lanthanum addition

The thermal stability of porous sol-gel phosphosilicates was studied by comparing the textural features upon calcination between 400 and 550 °C. A significant loss of surface area and pore volume were observed; the first is due to thermal coarsening of the nanoparticles, and the pore volume reduction was ascribed to sintering of the most external nanoparticles producing less void volume. Lanthanum addition was investigated as thermal stabilizer. For the mesoporous phosphosilicate composition, lanthanum addition enhanced the surface area, showing a 45% and 50% improvement with respect to the La-free counterpart; the effect was much less visible for the macroporous composition.

Tail gas catalyzed N2O decomposition over Fe-beta zeolite. On the promoting role of framework connected AlO6 sites in the vicinity of Fe by controlled dealumination during exchange

A novel route to prepare highly active and stable N2O decomposition catalysts is presented, based on Fe-exchanged beta zeolite. The procedure consists of liquid phase Fe(III) exchange at low pH. By varying the pH systematically from 3.5 to 0, using nitric acid during each Fe(III)-exchange procedure, the degree of dealumination was controlled, verified by ICP and NMR. Dealumination changes the presence of neighbouring octahedral Al sites of the Fe sites, improving the performance for this reaction. The so-obtained catalysts exhibit a remarkable enhancement in activity, for an optimal pH of 1. Further optimization by increasing the Fe content is possible. The optimal formulation showed good conversion levels, comparable to a benchmark Fe-ferrierite catalyst. The catalyst stability under tail gas conditions containing NO, O2 and H2O was excellent, without any appreciable activity decay during 70 h time on stream. Based on characterisation and data analysis from ICP, single pulse excitation NMR, MQ MAS NMR, N2 physisorption, TPR(H2) analysis and apparent activation energies, the improved catalytic performance is attributed to an increased concentration of active sites. Temperature programmed reduction experiments reveal significant changes in the Fe(III) reducibility pattern with the presence of two reduction peaks; tentatively attributed to the interaction of the Fe-oxo species with electron withdrawing extraframework AlO6 species, causing a delayed reduction. A low-temperature peak is attributed to Fe-species exchanged on zeolitic AlO4 sites, which are partially charged by the presence of the neighbouring extraframework AlO6 sites. Improved mass transport phenomena due to acid leaching is ruled out. The increased activity is rationalized by an active site model, whose concentration increases by selectively washing out the distorted extraframework AlO6 species under acidic (optimal) conditions, liberating active Fe species.