With the progress in medicine, the average human life expectancy is continuously increasing. At the same time, the number of patients who require full organ transplantations is augmenting. Consequently, new strategies for cell transplantation are the subject of great interest.This work reports the design, the synthesis and the characterisation of robust and biocompatible mineralised beads composed of two layers: an alginate-silica composite core and a Ca-alginate layer. The adequate choice of materials was achieved through cytotoxicity LDH release measurement and in vitro inflammatory assay (IL-8) to meet the biocompatibility requirements for medical purpose. The results obtained following this strategy provide a direct proof of the total innocuity of silica and alginate networks for human cells as underscored by the non-activation of immune defenders (THP-1 monocytes). The accessible pore size diameter of the mineralised beads synthesized was estimated between 22 and 30 nm, as required for efficient immuno-isolation without preventing the diffusion of nutrients and metabolites. The model human cells, HepG2, entrapped within these hybrid beads display a high survival rate over more than six weeks according to the measurements of intracellular enzymatic activity, respiration rate, as well as the "de novo" biosynthesis and secretion of albumin out of the beads.The current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system. The functionality of the cell strain can be maintained. Consequently, cells coated with an artificial and a biocompatible mineral shell could respond physiologically within the human body in order to deliver therapeutic agents in a controlled fashion (i.e. insulin), substituting the declining organ functions of the patient.
Venous stasis is a situation encountered commonly in varicose disorders. The potential implications of this decrease in oxygen levels in terms of the status of the cells of the vein were assessed. When endothelial cells are subjected to hypoxia, there is stimulation of the cells which shows itself as increased synthesis of prostaglandins and of PAF (Platelet Activating Factor). The synthesis of these typical mediators of inflammation results from activation by the calcium of phospholipase A2 which releases the arachidonic acid of phospholipids and this increase in intracellular calcium results itself from a fall in efficacy of calcium pumps due to the fall in ATP caused by hypoxia. Thus the fall in oxygen leads to the production of mediators of inflammation which activate leucocytes and result in local micro-inflammation which can be very rapidly eliminated if the circulation is restored but which can also cause irreversible damage to the vein by changes in venous tissue due to activated leucocytes which release proteases and free radicals after having penetrated the intima of the vein. These processes offer an explanation for the histological changes seen in varicose veins and the onset of localised pain during the development of such disease.
Epidermoid carcinoma model cell lines overexpressing epidermal growth factor receptor (EGFR+) can be sorted off and selectively killed from a population of a “healthy” (EGFR-) cell line. On page 3173, Davide Bonifazi and co-workers report that this is due to the combined action of the conjugated targeting antibody and the Fe-filled carbon nanotubes, with the latter exerting a magnetic fluid hyperthermia.
Hypoxia-inducible transcription factor 1alpha (HIF-1alpha) is a key player in the response to hypoxia. Additionally, HIF-1alpha responds to growth factors and hormones which can act via protein kinase B (Akt). However, HIF-1alpha is not a direct substrate for this kinase. Therefore, we investigated whether the protein kinase B target glycogen synthase kinase 3 (GSK-3) may have an impact on HIF-1alpha. We found that the inhibition or depletion of GSK-3 induced HIF-1alpha whereas the overexpression of GSK-3beta reduced HIF-1alpha. These effects were mediated via three amino acid residues in the oxygen-dependent degradation domain of HIF-1alpha. In addition, mutation analyses and experiments with von Hippel-Lindau (VHL)-defective cells indicated that GSK-3 mediates HIF-1alpha degradation in a VHL-independent manner. In line with these observations, the inhibition of the proteasome reversed the GSK-3 effects, indicating that GSK-3 may target HIF-1alpha to the proteasome by phosphorylation. Thus, the direct regulation of HIF-1alpha stability by GSK-3 may influence physiological processes or pathophysiological situations such as metabolic diseases or tumors.
