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Biomedical subjects

C Rastellini

Publications and source records attributed to C Rastellini.

At least 37 records · Page 2Linked to original sources
PubMed1995

Granulocyte/macrophage colony-stimulating factor-stimulated hepatic dendritic cell progenitors prolong pancreatic islet allograft survival.

Liver-derived dendritic cell (DC) progenitors propagated in liquid culture in granulocyte/macrophage colony-stimulating factor exhibit low levels both of cell surface MHC class II antigens and of counter-receptors for CTLA-4/CD28. They fail to stimulate allogeneic T cells in mixed leukocyte cultures. To evaluate their in vivo functional significance, we determined their influence on survival of pancreatic islet allografts. Cultured B10.BR (H2k;I-E+) mouse liver-derived DC progenitors were injected (2 x 10(6) i.v.) into streptozotocin-diabetic B10 (H2b; I-E-) recipients 7 days before transplantation of pancreatic islets (700 IEq/mouse) from the same donor strain. No immunosuppressive agents were administered. Mean islet allograft survival time was prolonged from 15.3 days (in animals pretreated with syngeneic cells) to 30.3 days (P < 0.001) in mice pretreated with the donor-derived liver cells. In 20% of these animals, islet allograft survival exceeded 60 days. These data suggest that liver-derived DC progenitors may contribute both to the inherent tolerogenicity of the mouse liver and to its capacity to protect other allografts of the same donor strain from rejection.

Animals↗
PubMedDate not supplied

Effect of perioperative antioxidant therapy on suboptimal islet transplantation in rats.

Islet transplantation success is limited by the posttransplant inflammatory response, and we are investigating the ability of antioxidants to neutralize this islet damage. We have shown that pyruvate can enhance the engraftment and functionality of a suboptimal islet mass in rats. The present study further investigated the effects of pyruvate, as well as the antioxidants vitamin E and vitamin C. In study A, 350 syngeneic islets were transplanted into the liver of chemically diabetic rats. Antioxidant treatment, or vehicle, was administered during the perioperative period and an intraperitoneal glucose tolerance test (IPGTT) was performed 2 months posttransplant. In study B, 500 syngeneic islets were transplanted under the kidney capsule of chemically diabetic rats. Antioxidant treatment was administered during the perioperative period. Islet-bearing kidney grafts were harvested 24, 48, and 96 hours posttransplant for histological study. Results revealed that pyruvate was the only significantly effective treatment in enhancing the engraftment and functionality of a suboptimal islet mass. Respectively, 56% and 80% of pyruvate-treated rats became normoglycemic after islet transplantation in study A and study B and had a normal insulin response to IPGTT. Histology results from the islet-bearing kidneys were inconclusive as to whether or not pyruvate has an antiapoptotic effect. We conclude that pyruvate, but not vitamin E or vitamin C, aids in the engraftment and functionality of a suboptimal islet mass with as much effectiveness as a full mass in this study. Further investigation into the mechanism of pyruvate protection is still warranted.

Animals↗
PubMedDate not supplied

Successful incorporation of short-interfering RNA into islet cells by in situ perfusion.

UNLABELLED: Islet transplantation offers a potential cure for type I diabetes, although its success has been limited, due to loss of cells by apoptosis stimulated by the procurement, ischemia, and the isolation process itself. RNA interference (RNAi) as mediated by short interfering RNAs (siRNAs) has become a potent tool to manipulate gene expression in mammalian cells. We describe the first successful introduction of siRNA directly into pancreatic islet cells both during in situ perfusion and from intravenous tail vein injection (in vivo). METHODS: siRNA was targeted to the pancreatic islets of BALB/c mice by retrograde portal vein perfusion or tail vein injection. Cy3-labeled siRNA was dissolved in University of Wisconsin (UW) solution at 2 microg/mL. After delivery pancreata were placed in cold storage at 4 degrees C in UW solution for 24 hours, followed by processing for immunofluorescent staining for insulin. Fluorescent imaging was obtained using a Nikon DIAPHOT 300 Inverted Micoscope with a Zeiss AxioCam and OpenLab image capturing software. RESULTS: In situ delivery of siRNA was demonstrated by fluorescent imaging composites of (red) siRNA in and along (green) insulin stained islets from pancreas sections as compared with untreated control sections. The siRNA was detected mainly in and along venous structures throughout the pancreatic tissue. In vivo delivery of siRNA into islets was observed by fluorescent images taken of isolated islets in culture. CONCLUSIONS: We have described the successful delivery of siRNA to pancreatic islets via a novel in situ pancreas perfusion technique and in vivo delivery via tail vein injection.

Adenosine↗
PubMedDate not supplied

A novel approach for intestinal elongation using acellular dermal matrix: an experimental study in rats.

We tested the hypothesis that an anatomic scaffold placed in continuity with viable bowel might allow intestinal growth. Male ACI rats were used for the study. Acellular human dermis in the form of tubular scaffolds with an intraluminal diameter of approximately 0.3 cm was oriented with the luminal basement membrane and serosal dermal surface. The small bowel was transected approximately 2 cm distal to the ligament of Treitz. The graft was then anastomosed in continuity in group A (n = 5) or as a blind-ended pouch to a defunctionalized jejunal limb in group B (n = 8). The animals were sacrificed at various time points. Histology and immunohistochemistry were used to evaluate structural changes. Animals in group A developed peritonitis and were all sacrificed within the first week postoperatively. However, all animals in group B survived, increasing their body weight similarly to age-matched rats. Tissue samples obtained at sacrifice showed a progressively increasing amount of cellular infiltrate over time in the matrix. Epithelial regeneration, angioneogenesis, and myofibroblast infiltrate were seen at 2 weeks, while well-formed branching crypts were seen at 4 weeks. Intact mucosa extended across the anastomosis to the grafts at 6 months. This study demonstrated an anatomic scaffold of acellular matrix allowed mucosal regeneration from viable bowel placed in continuity. These findings set the basis for new intestinal elongation techniques.

Anastomosis, Surgical↗