Aims/hypothesis
Islet transplantation is a promising treatment for type 1 diabetes but is hampered by a shortage of donor human tissue and early failure. Research on islet-cell transplantation includes finding new sources of cells and immunoisolation to protect from immune assault and tumorigenic potential. Small islet-cell aggregates were studied to determine if their survival and function were superior to intact islets within microcapsules because of reduced oxygen transport limitation and inflammatory mediators.
Methods
Islet-cell aggregates were generated by dispersing rat islets into single cells and allowing them to re-aggregate in culture. Rat islets and islet-cell aggregates were encapsulated in barium alginate capsules and studied when cultured in low (0.5% or 2%) or normal (20%) oxygen, or transplanted into mice.
Results
Encapsulated islet-cell aggregates were able to survive and function better than intact islets in terms of oxygen-consumption rate, nuclei counts, insulin-to-DNA ratio, and glucose-stimulated insulin secretion. They also had reduced expression of pro-inflammatory genes. Islet-cell aggregates showed reduced tissue necrosis in an immunodeficient transplant model and a much greater proportion of diabetic xenogeneic transplant recipients receiving islet-cell aggregates (tissue volume of only 85 islet equivalents) had reversal of hyperglycaemia than recipients receiving intact islets.
Conclusions/interpretation
These aggregates were superior to intact islets in terms of survival and function in low-oxygen culture and during transplantation and are likely to provide more efficient utilisation of islet tissue, a finding of importance for the future of cell therapy for diabetes.
Coral reefs comprise a variety of microhabitats, each with a characteristic pattern of water movement. Variation in flow microhabitat is likely to influence the distribution and abundance of suspension feeders, including the corals. Water flow was measured concurrently with wave heights at 8 depths along the forereef slope in Salt River Canyon, St Croix, U.S.V.I. The greatest flow speeds occurred on the shallow forereef at 7 m depth, where oscillatory wave-induced flow reached speeds over 50 cm s-'. From 7 m to at least 15 m depth, flow decreased and was primarily bidirectional. Below 15 m depth, flow decreased even further, to less than one fifth of that experienced by shallow corals, and was unidirectional. The relationship between particle capture by the corals Meandrina meandrites and Madracis decactis and water flow was studied in the field. Colony morphology and the resulting modification of flow influenced the relationship of flow to feeding success; prey capture by the branching Madracis colonies increased with flow, while that of the flat Meandrina colonies did not. Such relationships may contribute to differences in distribution of corals of divergent morphologies. In transect surveys from 7 to 45 m depth,; branching and mounding corals with tentacular feeding modes were most common in the shallow forereef habitats, and plating corals with small polyps (ciliary mucus feeders) were ubiquitous in the deeper zones.
Sea urchin skeletons are strengthened by flexible collagenous ligaments that bind together rigid calcite plates at sutures. Whole skeletons without ligaments (removed by bleaching) broke at lower apically applied forces than did intact, fresh skeletons. In addition, in three-point bending tests on excised plate combinations, sutural ligaments strengthened sutures but not plates. The degree of sutural strengthening by ligaments depended on sutural position; in tensile tests, ambital and adapical sutures were strengthened more than adoral sutures. Adapical sutures, which grow fastest, were also the loosest, suggesting that strengthening by ligaments is associated with growth. In fed, growing urchins, sutures overall were looser than in unfed urchins. Looseness was demonstrated visually and by vibration analysis: bleached skeletons of unfed urchins rang at characteristic frequencies, indicating that sound traveled across tightly fitting sutures; skeletons of fed urchins damped vibrations, indicating loss of vibrational energy across looser sutures. Furthermore, bleached skeletons of fed urchins broke at lower apically applied forces than bleached skeletons of unfed urchins, indicating that the sutures of fed urchins had been held together relatively loosely by sutural ligaments. Thus, the apparently rigid dome-like skeleton of urchins sometimes transforms into a flexible, jointed membrane as sutures loosen and become flexible during growth.
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