Diannexin decreases inflammatory cell infiltration into the islet graft, reduces β-cell apoptosis, and improves early graft function.

Transplantation
Elaine Y ChengHua Yang

Abstract

A major unmet challenge is to reduce the islet mass needed for insulin independence in type 1 diabetic recipients after islet transplantation. The recombinant homodimer of human annexin V, diannexin, has completed a Phase II Clinical Trial in Kidney Transplantation (NCT00615966). We developed a marginal islet mass transplantation model (10-12 islets per gram of recipient body weight) and investigated whether diannexin prevents β-cell apoptosis and improves islet graft function. Diannexin was administered to islet cell donors shortly before pancreas harvest, added to isolation reagents, and infused into recipients at the time of transplantation and repeated daily until day 4. In the syngeneic marginal islet mass transplantation model, the median time needed to achieve normoglycemia was reduced from 17.0 days among untreated controls to 3.5 days among diannexin-treated recipients (P=0.004). Histologic analysis of islet grafts harvested on day 3 posttransplantation revealed decreased macrophage (44.7%±9.8% vs. 19.2%±3.2%, P=0.007) and T-cell infiltration (25.9%±5.5% vs. 9.1%±1.1%, P=0.004), and a lower rate of islet cell apoptosis (20.5%±2.8% vs. 7.6%±2.3%, P=0.01) with diannexin treatment. Expression profiling of the islet grafts...Continue Reading

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Citations

Nov 3, 2011·Journal of Transplantation·Preeti Chhabra, Kenneth L Brayman
Jan 5, 2016·The Journal of Thoracic and Cardiovascular Surgery·Kohei HashimotoShaf Keshavjee
Jan 15, 2014·Current Problems in Surgery·Preeti Chhabra, Kenneth L Brayman
Jun 3, 2014·International Journal of Endocrinology·Mazhar A KanakBashoo Naziruddin
Jan 16, 2014·The Journal of Clinical Endocrinology and Metabolism·Filiz BakarSerpil Nebioğlu
Jun 15, 2011·Current Opinion in Organ Transplantation·Keri E LunsfordTodd V Brennan
Jul 14, 2021·Experimental Biology and Medicine·Frans A KuypersClaudia R Morris
Aug 19, 2021·Apoptosis : an International Journal on Programmed Cell Death·Akvile HaeckelEyk Schellenberger

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