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Riccardo Calafiore

Publications and source records attributed to Riccardo Calafiore.

4 recordsLinked to original sources

Multifunctional microcapsules for pancreatic islet cell entrapment: design, preparation and in vitro characterization.

Great advances in cell transplantation have been made, including the recent, remarkable success in pancreatic islet transplantation for the treatment of type 1 diabetes mellitus. Unfortunately, the transplanted cells are very susceptible to oxidative stress that cause severe damage to either allo- or xenogeneic islets upon graft in diabetic patients. Consequently, the transplanted islet functional life span is significantly shortened. The aim of this study was to examine the possible effects of antioxidants on in vitro cultured adult rat islets, and to evaluate the effects of a prolonged-release formulation, in form of cellulose acetate (CA) microspheres, on Vitamin D(3) activity. Isolated rat islets, both free and entrapped in microspheres were treated with Vitamin D(3). The effects of the vitamin were studied at 3, 6 and 9 days of in vitro cell culture. According to insulin secretory patterns, treatment with Vitamin D(3) of both free and CA entrapped microspheres, increased the insulin output as compared to untreated controls. Such positive effects were confirmed under islet static incubation with glucose at day 6. These results suggest that pancreatic islets can be advantageously treated with anti-oxidising vitamins before implantation, and speculatively, with the help of special delivery systems, throughout the islet cell life span, in the post-transplant time period.

Animals↗

Mitogenic effects of Brazilian arthropod venom on isolated islet beta cells: in vitro morphologic ultrastructural and functional studies.

BACKGROUND: One of the major pitfalls associated with use of isolated adult islets of Langerhans' cells is their minimal mitotic capacity. Consequently, maintenance of a steady viable islet cell mass is very difficult. To explore how to enhance beta-cell mitogenesis, we have examined the effects of venom fractions extracted from a Brazilian scorpion on morphologic and functional beta-cell patterns. The venom was previously known to induce nesidioblastosis-like effects with chronic hypoglycemia and pancreatitis in animal models. METHODS: Venom fractions purified from Tityus bahiensis were incubated with batches of isolated rat islets, while a morphologic examination, glucose-stimulated insulin release, insulin content, and insulin messenger ribonucleic acid (mRNA) were carried out early during incubation. On fixation and double fluorescence immunolabeling (rhodamine for anti-insulin monoclonal antibodies; fluorescein for anti-5-bromodeoxyuridine), the preparations were imaged by confocal laser microscopy (CLM) for morphometric quantification of the mitoses. Insulin recovery and mRNA were also assessed at 21 days of culture. RESULTS: Under CLM examination, the beta-cell mitotic rate significantly rose from 1 to 12.8% for the venom-exposed islets. At day 7, insulin release and content were significantly lower for the venom-exposed than the control islets. However, at day 21 of culture, insulin release in response to static incubation with glucose and insulin mRNA from the venom-exposed islets was higher than controls (p < .05). CONCLUSIONS: Incubation with the scorpion venom induced a rapid and significant increase in the beta-cell proliferation not associated with a short-term increase in insulin secretion. The latter fully resumed and overcame controls later in culture, possibly after completion of the beta-cell expansion process.

Animals↗

Alginate microcapsules for pancreatic islet cell graft immunoprotection: struggle and progress towards the final cure for type 1 diabetes mellitus.

Lights and shadows have been associated with the use of alginate/polyaminoacidic microcapsules for transplantation of pancreatic islet cells for the therapy of diabetes mellitus, with no recipient pharmacological immunosuppression. In fact, preliminary success in rodents has generally not matched the results achieved in diabetic higher mammals. The restricted availability of cadaveric human donor organs/tissue, coupled to regulatory hurdles in the use of microcapsules in patients, has significantly delayed the progress of microencapsulated islet grafts into pilot clinical trials. While the basic formulation of microcapsules from the author's laboratory, originally comprised of an alginate gel (AG) core, a double poly-L-ornithine (PLO) coat and an outer AG coat, has virtually remained unchanged, highly purified 'clinical grade' AG has been introduced in order to try to surmount regulatory restrictions. In parallel, novel insulin-producing cell types have been employed to fill the capsules, with particular regard to non-human tissue, such as adult and, more recently, neonatal porcine islets. In particular, using neonatal porcine islets enveloped in AG-PLO microcapsules, hyperglycaemia has been corrected in several diabetic animal models. Should standardisation and optimisation problems associated with both AG procurement and other membrane physical-chemical fabrication parameters be surmounted, microcapsules containing either human or, possibly, pig islets, could be close to approval for Phase I human clinical trials.

Alginates↗