Journal ArticleDOI
Vulnerability of Islets in the Immediate Posttransplantation Period: Dynamic Changes in Structure and Function
Alberto M. Davalli,Luisa Scaglia,David Zangen,Jennifer Hollister,Susan Bonner-Weir,Gordon C. Weir +5 more
TLDR
The first few days of islet transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, with substantial islet cell dysfunction and death followed by tissue remodeling and then stable engraftment.Abstract:
To learn more about islet vulnerability in the immediate posttransplant period, 400 syngeneic islets were transplanted under the kidney capsule of B6AF1 mice. Three groups of recipients were used: normal mice (normal), streptozotocin (STZ)-diabetic (diabetic), and STZ-diabetic kept hypo- or normoglycemic with insulin pellets (diabetic-normalized). Normoglycemia was achieved in all three groups 14 days after transplantation; however, in the diabetic and diabetic-normalized groups, blood glucose levels throughout the posttransplantation period were respectively higher and lower than in the normal group. Grafts were harvested 1, 3, 7, and 14 days after transplantation and analyzed for morphology, beta-cell death, beta-cell mass, insulin content, and insulin mRNA expression. In all groups, substantial damage in islet grafts was found on days 1 and 3 with apoptotic nuclei and necrotic cores; on day 3, beta-cell death was significantly higher in the diabetic group than in the other groups. Tissue remodelling occurred in all groups with stable graft appearance on day 14; the actual beta-cell mass of the grafts was lowest in the diabetic group. Graft insulin content decreased in all groups on day 1 and fell even further on days 3 and 7. Insulin mRNA levels of grafts retrieved from both the diabetic and diabetic-normalized group were lower than those from the normal group already by day 1 and remained lower on day 14. In conclusion, the first few days of islet transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, with substantial islet cell dysfunction and death followed by tissue remodelling and then stable engraftment.read more
Citations
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Journal ArticleDOI
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells
TL;DR: New evidence is provided that rapamycin selectively expands the murine naturally occurring CD4(+)CD25(+)FoxP3(+) Tr cells in vitro, and this new mode of action can be used to expand CD4 (+) CD25 (+) FoxP3 (%) Tr cells for ex vivo cellular therapy in T-cell-mediated diseases.
Journal ArticleDOI
Regulatory T Cells Induced by 1α,25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance
Silvia Gregori,Mara Casorati,Susana Amuchastegui,Simona Smiroldo,Alberto M. Davalli,Luciano Adorini +5 more
TL;DR: It is demonstrated that a short treatment with immunosuppressive agents, such as 1α,25-dihydroxyvitamin D3/mycophenolate mofetil, induces tolerance to islet allografts associated with an increased frequency of CD4+CD25+ regulatory cells that can adoptively transfer transplantation tolerance.
Journal ArticleDOI
Abnormal angiogenesis in diabetes mellitus.
TL;DR: In this review, the clinical features, molecular mechanisms, and potential therapeutic options of abnormal angiogenesis in diabetes will be reviewed.
Journal ArticleDOI
Pancreatic Islet Production of Vascular Endothelial Growth Factor-A Is Essential for Islet Vascularization, Revascularization, and Function
Marcela Brissova,Alena Shostak,Masakazu Shiota,Peter O. Wiebe,Greg Poffenberger,Jeannelle Kantz,Zhongyi Chen,Chad Carr,W. Gray Jerome,Jin Chen,H. Scott Baldwin,Wendell E. Nicholson,David M. Bader,Thomas L. Jetton,Maureen Gannon,Alvin C. Powers +15 more
TL;DR: The genetic data indicate that vascular endothelial growth factor (VEGF)-A is a major regulator of islet vascularization and revascularization of transplanted islets and that the microvasculature plays an integral role in islet function.
Journal ArticleDOI
β-Cell Death and Mass in Syngeneically Transplanted Islets Exposed to Short- and Long-Term Hyperglycemia
TL;DR: Even in optimal conditions, approximately 60% of transplanted islet tissue was lost 3 days after syngeneic transplantation, and both apoptosis and necrosis contributed to beta-cell death, suggesting that sustained hyperglycemia increased apoptosis in transplanted beta-cells.
References
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Book
Molecular Cloning: A Laboratory Manual
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
Journal ArticleDOI
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
TL;DR: In this article, a technique for conveniently radiolabeling DNA restriction endonuclease fragments to high specific activity is described, where DNA fragments are purified from agarose gels directly by ethanol precipitation and are then denatured and labeled with the large fragment of DNA polymerase I, using random oligonucleotides as primers.
Journal ArticleDOI
Apoptosis: the biochemistry and molecular biology of programmed cell death.
TL;DR: This review first briefly covers some historical perspective on the discovery of apoptotic cell death, the characteristic morphology that accompanies this process, and the numerous cell types and mediators with which programmed cell death is associated.
Journal ArticleDOI
Programmed cell death and Bcl-2 protection in very low oxygen.
Michael D. Jacobson,Martin Raff +1 more
TL;DR: It is found that cells cultured in a near-anaerobic atmosphere where the generation of ROS would be expected not to occur, or at least to be greatly reduced, inhibit PCD induced by ROS-generating agents but do not inhibit PCd induced by other means.