Pancreatic Duct Cells in Human Islet Cell Preparations Are a Source of Angiogenic Cytokines Interleukin-8 and Vascular Endothelial Growth Factor

OBJECTIVE—Engraftment and function of human islet cell implants is considered to be dependent on their rapid and adequate revascularization. Studies with rodent islet grafts have shown that vascular endothelial growth factor (VEGF) expression by β-cells can promote this process. The present work examines whether human islet preparations produce VEGF as well as interleukin (IL)-8, another angiogenic protein, and assesses the role of contaminating duct cells in VEGF and IL-8–mediated angiogenesis

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes

AIMS/HYPOTHESIS: As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function. METHODS: Human BOEC, 5 × 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated. RESULTS: Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient. CONCLUSIONS/INTERPRETATION: The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.status: publishe

Predictive Factors of Allosensitization After Immunosuppressant Withdrawal in Recipients of Long-Term Cultured Islet Cell Grafts

Transplantation and autoimmunit

Kidney transplantation after rescue allocation : the Eurotransplant experience : a retrospective multicenter outcome analysis

Background: At Eurotransplant (ET), kidneys are transferred to 'rescue allocation' (RA), whenever the standard allocation (SA) algorithms Eurotransplant kidney allocation system (ETKAS) and Eurotransplant senior program (ESP) fail. We analyzed the outcome of RA. Methods: Retrospective patient clinical and demographic characteristics association analyses with graft outcomes for 2,421 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25,475 after SA from 71 centers across all ET countries from 2006 to 2018. Results: Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP vs. ETKAS (2.7% vs. 10.4%). RA recipients and donors were older compared to SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary non-function was comparable. Among ETKAS-recipients, HLA matching was more favorable in SA (mean 3.7 vs. 2.5). In multivariate modeling, the incidence of death with a functioning graft (DwFG) in ETKAS was reduced in RA compared to SA (subdistribution hazard ratio 0.70, 95% confidence interval [0.60-0.81], p<0.001) whereas other outcomes (mortality, graft loss) were not significantly different. None of the three outcomes were significantly different when comparing RA with SA within the ESP program. Conclusions: Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.Supplemental Visual Abstract; http://links.lww.com/TP/C297