Home About us Contact
|
Home About us Contact | ||
|
|
||
Islet Grafts (islet + graft)
Selected AbstractsEvidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Kessler We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex® screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex® tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free. [source] Combined Coinhibitory and Costimulatory Modulation with Anti-BTLA and CTLA4Ig Facilitates Tolerance in Murine Islet AllograftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007W. Truong Complex interactions between positive and negative cosignaling receptors ultimately determine the fate of the immune response. The recently identified coinhibitory receptor, B and T lymphocyte attenuator (BTLA), contributes to regulation of autoimmune and potentially alloimmune responses. We investigated the role of BTLA in a fully major histocompatibility complex-mismatched mouse islet transplant model. We report that anti-BTLA mAb (6F7) alone does not accelerate graft rejection. Rather, while CTLA4Ig alone improved allograft survival, the addition of anti-BTLA mAb to CTLA4Ig led to indefinite (>100 days) allograft survival. Immediately after treatment with anti-BTLA mAb and CTLA4Ig, islet allografts showed intact islets and insulin production despite a host cellular response, with local accumulation of Foxp3+ cells. We clearly demonstrate that combined therapy with anti-BTLA mAb and CTLA4Ig mice induced donor-specific tolerance, since mice accepted a second donor-specific islet graft without further treatment and rejected third party grafts. CTLA4Ig and anti-BTLA mAb limited the initial in vivo proliferation of CFSE-labeled allogeneic lymphocytes, and anti-BTLA mAb enhanced the proportion of PD-1 expressing T cells while depleting pathogenic BTLA+ lymphocytes. We conclude that targeting the BTLA pathway in conjunction with CTLA4Ig costimulatory blockade may be a useful strategy for promoting immunological tolerance in murine islet allografts. [source] Composite Islet-Endothelial Cell Grafts: A Novel Approach to Counteract Innate Immunity in Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005Ulrika Johansson An instant blood-mediated inflammatory reaction (IBMIR) is elicited when islets come in contact with blood after intraportal transplantation. In contrast, endothelial cells (EC) readily tolerate contact with blood. A conceivable strategy to overcome IBMIR would be to create composite islet-EC grafts. Human islets were co-cultured with primary human aortic endothelial cells (HAEC) for 2,7 days to obtain 50,90% coverage. HAEC-coated islets were exposed to ABO-identical blood and analyzed with regard to clotting time, signs of inflammation and cell infiltration. Composite islet-HAEC graft survival was assessed after transplantation to athymic (nu/nu) nude mice. Exposed to blood, HAEC-coated islets induced less activation of coagulation and complement compared to control islets. Also, platelet and leukocyte consumption in blood was decreased. Clots with entrapped HAEC-coated islets showed less infiltration of CD11b+ cells. The extent of protection correlated to the level of HAEC coverage. Transplanted composite grafts stained positive for insulin and PECAM-1 demonstrating presence of both islets and HAEC within the islet graft 7 weeks after transplantation. Composite islet-HAEC grafts reduce all components of IBMIR. Refinement of the technique will allow introduction of composite islet-EC grafts in clinical islet transplantation, using autologous EC expanded in vitro and kept frozen until allogeneic islets become available for that specific recipient. [source] Cotransplanted hepatic stellate cells enhance vascularization of islet allograftsMICROSURGERY, Issue 4 2007Zhenyu Yin M.D. Islet transplantation is an alternative to whole pancreas transplantation in curative therapy of diabetics. The outcome of engraftment of islet, however, remains disappointing. Rapid and adequate islet revascularization is crucial for the survival and function of transplanted islets. In this study, hepatic stellate cells (HSC) were cotransplanted with islet allografts, achieving marked prolongation of islet allografts. This was associated with enhanced revascularization within islet grafts as determined by anti-CD31 antibody staining. © 2007 Wiley-Liss, Inc. Microsurgery 2007. [source] TLR4 Mediates Early Graft Failure After Intraportal Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010Q. Gao We have previously shown that islet emboli in the portal vein block blood flow and induce local inflammatory reaction, resulting in functional loss of islet grafts following intraportal transplantation. This study was designed to test whether Toll-like receptor (TLR) activation mediates early islet graft failure. Syngeneic islet grafts were transplanted into chemically induced diabetic mice, and TLR deficient mice were used as donors and/or recipients of islet grafts. Islet viability, proinflammatory cytokines, high-mobility group box-1 (HMGB1) and NF-,B activation were analyzed by bioluminesce imaging (BLI), quantitative RT-PCR (qRT-PCR) and histology. Early islet graft failure was observed in mice with intraportal islet engrafts with increased proinflammatory cytokines, HMGB1 expression, NF-,B activation, caspase-3 and TUNEL positive cells. Deficiency of TLR4 in donor, but not in recipient, inhibited NF-,B activation, reduced proinflammatory cytokines and improved viability of islet grafts. Blockade of HMGB1 with anti-HMGB1 monoclonal antibody (mAb, 2g7) inhibited inflammatory reactions, as evidenced by reduced TNF, and IL-1ß production, and improved islet viability. We conclude that TLR4 activation mediates early graft failure following intraportal islet transplantation. Inhibition of TLR4 activation represents a novel strategy to attenuate early graft failure following intraportal islet transplantation. [source] Lymphatic Vessels in Pancreatic Islets Implanted Under the Renal Capsule of RatsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006Ö. Källskog Transplantation of pancreatic islets necessitates an engraftment process, including revascularization of the graft. Studies of graft vasculature have demonstrated that islets become revascularized during the first post-transplant week through an angiogenic process. If this also involves lymphatic vessels is unknown. The aim of the present study was to functionally evaluate if lymphatic vessels, which are absent in endogenous islets, form after islet transplantation. To achieve this, inbred Wistar-Furth rats were transplanted with 250 syngeneic islets under the renal capsule. Intra-vital microscopy of the graft in combination with interstitial injection of Evans Blue was performed 1 week, 1 month or 9,12 months later. In all animals studied, there was drainage through intra-graft lymphatic capillaries emptying into larger lymphatic vessels associated with the renal capsule. The number was slightly lower 1 week post-transplantation. Most of the lymphatic capillaries were present in the graft stroma, rather than interspersed among the endocrine cells. In some animals, we were able to demonstrate dye in regional lymph nodes. We conclude that unlike endogenous islets, islet grafts develop a lymphatic drainage. Its functional importance and characteristics remain to be established. However, it can be speculated that immune reactions may be facilitated by the presence of lymphatic vessels. [source] Entrapment of dispersed pancreatic islet cells in CultiSpher-S macroporous gelatin microcarriers: Preparation, in vitro characterization, and microencapsulationBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2001S. Del Guerra Abstract Immunoprotection of pancreatic islets for successful allo- or xenotransplantation without chronic immunosuppression is an attractive, but still elusive, approach for curing type 1 diabetes. It was recently shown that, even in the absence of fibrotic overgrowth, other factors, mainly insufficient nutrition to the core of the islets, represent a major barrier for long-term survival of intraperitoneal microencapsulated islet grafts. The use of dispersed cells might contribute to solve this problem due to the conceivably easier nutritional support to the cells. In the present study, purified bovine islets, prepared by collagenase digestion and density gradient purification, and dispersed bovine islet cells, obtained by trypsin and DNAsi (viability > 90%), were entrapped into either 2% (w/v) sodium alginate (commonly used for encapsulation purposes) or (dispersed islet cells only) macroporous gelatin microcarriers (CulthiSpher-S, commonly used for the production of biologicals by animal cells). Insulin release studies in response to glucose were performed within 1 week and after 1 month from preparation of the varying systems and showed no capability of dispersed bovine islet cells within sodium alginate microcapsules to sense glucose concentration changes. On the contrary, bovine islet cells entrapped in CulthiSpher-S microcarriers showed maintained capacity of increasing insulin secretion upon enhanced glucose concentration challenge. In this case, insulin release was approximately 60% of that from intact bovine islets within sodium alginate microcapsules. MTT and hematoxylineosin staining of islet cell-containing microcarriers showed the presence of viable and metabolically active cells throughout the study period. This encouraging functional data prompted us to test whether the microcarriers could be immunoisolated for potential use in transplantation. The microcarriers were embedded within 3% sodium alginate, which was then covered with a poly-L-lysine layer and a final outer alginate layer. Maintained insulin secretion function of this system was observed, which raises the possibility of using microencapsulated CulthiSpher-S microcarriers, containing dispersed pancreatic islet cells, in experimental transplantation studies. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 741,744, 2001. [source] | ||||||||||