Hybrid Shell Engineering of Animal Cells for Immune Protections and Regulation of Drug Delivery: Towards the Design of “Artificial Organs”

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

Dendroclimatological reconstructions in South America: a review

Recent years have seen a consolidation and expansion of tree-ring sample collection across South America. Most collections are concentrated in the temperate forests along the eastern and western slopes of the Southern Andes (32°S to 55°S). However, important advances in the reconnaissance and collection of new woody species useful for dendrochronology have recently been documented in new regions. The development of chronologies in tropical and subtropical arid regions of the Cordillera, and in particular the Bolivian Altiplano, is probably one of the most important recent advances in South American dendrochronology. Polylepis tarapacana, growing at 4000-4500 m elevation on the Altiplano, has yielded more than ten chronologies spanning the past 700 years. These records are highly correlated with summer variations in climate. The development of chronologies in the humid subtropics and tropics remains a major challenge. The number of tree-ring chronologies built up using species from these regions (ca. 40) is comparatively low in relation to the extent of tropical forests. The recognition of strong climate signals in tree rings from Cedrela species provides a unique opportunity to develop a tree-ring network in subtropical and tropical South America. The future of dendroclimatology in South American tropical regions is perceived as extremely promising. Reconstructions of temperature, rainfall, streamflow, snow and regional atmospheric circulation based on ring width, density and stable isotopes, have been conducted using tree-ring chronologies from subtropical and temperate forests. These chronologies have also been used in studies relating South American tree rings to high-resolution proxies from other continents, and studies analyzing past changes in atmospheric circulation. The comparison of climatic reconstructions based on tree rings with projected atmospheric circulation patterns provides a useful bridge between past and future trends in global climate change, and its implications for human welfare and socio-economic development. Some examples of this bridging are presented in this review. Future research should continue the development of long tree-ring chronologies to improve detection of decadal to centennial climatic variations and to distinguish between natural and human-induced climatic changes in South America. Efforts to develop new tree-ring chronologies in the tropical lowlands should also be encouraged. Collaboration among South American countries in training young scholars is crucial to maintain and increase the progress of dendroclimatology in the region. Initiatives facilitating the interaction between scientists from the Americas and overseas, such as done by the IAI and PAGES projects, should be broadened and their long-term continuation assured

Climate variability 50,000 years ago in mid-latitude Chile as reconstructed from tree rings

High-resolution proxies of past climate are essential for a better understanding of the climate system. Tree rings are routinely used to reconstruct Holocene climate variations at high temporal resolution, but only rarely have they offered insight into climate variability during earlier periods. Fitzroya cupressoides - a South American conifer which attains ages up to 3,600 years - has been shown to record summer temperatures in northern Patagonia during the past few millennia. Here we report a floating 1,229-year chronology developed from subfossil stumps of E cupressoides in southern Chile that dates back to approximately 50,000 14C years before present. We use this chronology to calculate the spectral characteristics of climate variability in this time, which was probably an interstadial (relatively warm) period. Growth oscillations at periods of 150-250, 87-94, 45.5, 24.1, 17.8, 9.3 and 2.7-5.3 years are identified in the annual subfossil record. A comparison with the power spectra of chronologies derived from living F. cupressoides trees shows strong similarities with the 50,000-year-old chronology, indicating that similar growth forcing factors operated in this glacial interstadial phase as in the current interglacial conditions

Unusual Southern Hemisphere tree growth patterns induced by changes in the Southern Annular Mode

Recent changes in the summer climate of the Southern Hemisphere extra-tropics are primarily related to the dominance of the positive phase of the Southern Annular Mode. This shift in the behaviour of the Southern Annular Mode—essentially a measure of the pressure gradient between Southern Hemisphere mid and high latitudes—has been predominantly induced by polar stratospheric ozone depletion. The concomitant southward expansion of the dry subtropical belts could have consequences for forest growth. Here, we use tree-ring records from over 3,000 trees in South America, Tasmania and New Zealand to identify dominant patterns of tree growth in recent centuries. We show that the foremost patterns of growth between 1950 and 2000 differed significantly from those in the previous 250 years. Specifically, growth was higher than the long-term average in the subalpine forests of Tasmania and New Zealand, but lower in the dry-mesic forests of Patagonia. We further demonstrate that variations in the Southern Annular Mode can explain 12–48% of the tree growth anomalies in the latter half of the twentieth century. Tree-ring-based reconstructions of summer Southern Annular Mode indices suggest that the high frequency of the positive phase since the 1950s is unprecedented in the past 600 years. We propose that changes in the Southern Annular Mode have significantly altered tree growth patterns in the Southern Hemisphere