Macroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin-producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber... Show moreMacroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin-producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber membranes are of interest there because they offer a large surface-to-volume ratio and can potentially be retrieved or refilled. However, current available fibers have limitations in exchange of nutrients, oxygen, and delivery of insulin potentially impacting graft survival. Here, multibore hollow fibers for islets encapsulation are designed and tested. They consist of seven bores and are prepared using nondegradable polymers with high mechanical stability and low cell adhesion properties. Human islets encapsulated there have a glucose induced insulin response (GIIS) similar to nonencapsulated islets. During 7 d of cell culture in vitro, the GIIS increases with graded doses of islets demonstrating the suitability of the microenvironment for islet survival. Moreover, first implantation studies in mice demonstrate device material biocompatibility with minimal tissue responses. Besides, formation of new blood vessels close to the implanted device is observed, an important requirement for maintaining islet viability and fast exchange of glucose and insulin. The results indicate that the developed fibers have high islet bearing capacity and can potentially be applied for a clinically applicable bioartificial pancreas. Show less
Calaminus, G.; Jenney, M.; Hjorth, L.; Baust, K.; Bernstein, M.; Bielack, S.; ... ; Nagarajan, R. 2019
The type of polymer influenced the functional survival of human islets. In islets cultured on PDLLCL the glucagon-producing alpha-cells and insulin-producing beta-cells contained more hormone... Show moreThe type of polymer influenced the functional survival of human islets. In islets cultured on PDLLCL the glucagon-producing alpha-cells and insulin-producing beta-cells contained more hormone granules than in islets in contact with PEOT/PBT or polysulfone. This was studied with ultrastructural analysis by electron microscopy (nanotomy) during 7 d of culture. PDLLCL was also associated with statistically significant lower release of double-stranded DNA (dsDNA, a so called danger-associate molecular pattern (DAMP)) from islets on PDLLCL when compared to the other polymers. DAMPs support undesired immune responses. Hydrophilicity of the polymers did not influence dsDNA release. Islets on PDLLCL also showed less cellular outgrowth. These outgrowing cells were mainly fibroblast and some beta-cells undergoing epithelial to mesenchymal cell transition. None of the polymers influenced the glucose-stimulated insulin secretion. As PDLLCL was associated with less release of DAMPs, it is a promising candidate for creating a scaffold for human islets. Our study demonstrates that for sensitive, rare cadaveric donor tissue such as pancreatic islets it might be necessary to first select materials that do not influence functionality before proposing the biomaterial for in vivo application. Our presented platform may facilitate this selection of biomaterials. Show less
Smink, A.; Haan, B.J. de; Paredes-Juarez, G.A.; Hertsig, D.T.; Marchioli, G.; Schwab, L.; ... ; Vos, P. de 2015
Rapidly growing global networking has induced and supported an increased interest in the life sciences in such general issues as health, climate change, food security and biodiversity. Therefore,... Show moreRapidly growing global networking has induced and supported an increased interest in the life sciences in such general issues as health, climate change, food security and biodiversity. Therefore, the need to address and share research data and materials in a systematic way emerged almost simultaneously. This movement has been described as the so-called global research commons. Also in microbiology, where the sharing of microbiological materials is a key issue, microbial commons is attracting attention. Microbiology is currently facing great challenges with the advances of high throughput screening and next-generation whole genome sequencing. Furthermore, the exploration and use of microorganisms in agriculture and food production are increasing so as to safeguard global food and feed production. Further to several meetings on the subject, a special issue of Research in Microbiology is dedicated to Microbial Research Commons with a series of reviews elaborating its major pay-offs and needs in basic and applied microbiology. This paper gives an introduction to these articles covering a range of topics. These include the role of public culture collections and biological resource centers and legal aspects in the exchange of materials, microbial classification, an internet-based platform for data-sharing, applications in agriculture and food production, and challenges in metagenomics and extremophile research. (C) 2010 Elsevier Masson SAS. All rights reserved. Show less
Aims Modification of lipoproteins plays an important role in the development of atherosclerosis. Oxidatively modified low-density lipoprotein (oxLDL) has a number of pro-inflammatory effects,... Show moreAims Modification of lipoproteins plays an important role in the development of atherosclerosis. Oxidatively modified low-density lipoprotein (oxLDL) has a number of pro-inflammatory effects, whereas immunization with various forms of oxLDL is able to reduce atherosclerosis. The uptake of modified LDL by dendritic cells (DCs) and the presentation of epitopes thereof may form an important step in the immunomodulatory effects of LDL. In this study, we transferred oxLDL-pulsed mature DCs (mDCs) to LDL receptor-null (LDLr-/-) mice and examined the effects on atherosclerosis. Methods and results Bone marrow-derived DCs were cultured for 10 days in the presence of granulocyte-macrophage colony-stimulating factor. Immature DCs were matured by lipopolysaccharide and pulsed with copper-oxidized LDL. These mDCs were transferred three times to LDLr-/- mice before the induction of atherosclerosis by Western-type diet feeding. The transfer of oxLDL-pulsed mDCs resulted in an 87% reduction in carotid artery lesion size (P < 0.001) with a concurrent increase in plaque stability, whereas treatment using mDCs pulsed with the atherosclerosis-irrelevant antigen, ovalbumin, did not influence lesion size or stability. Furthermore, the vaccination procedure resulted in the induction of oxLDL-specific T cells with a reduced Th1 profile and an increase in oxLDL-specific IgG levels, which contributed to a reduction in foam cell formation. Conclusion These data indicate that vaccination with oxLDL-pulsed mDCs provides a novel and powerful strategy for the immunomodulation of atherosclerosis. Show less
Out, R.; Kruijt, J.K.; Rensen, P.C.N.; Hildebrand, R.B.; Vos, P. de; Eck, M. van; Berkel, T.J.C. van 2004
