Gene transfer of anti-apoptotic Insulin-Like Growth Factor-Ii (Igf-Ii) to pancreatic islets offers a novel therapeutic strategy to improve islet cell survival post-transplanation — ASN Events
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Gene transfer of anti-apoptotic Insulin-Like Growth Factor-Ii (Igf-Ii) to pancreatic islets offers a novel therapeutic strategy to improve islet cell survival post-transplanation (#217)

Amy Hughes 1 2 , D Mohanasundaram 1 2 3 , Chris J Drogemuller 1 2 3 , Claire F Jessup 4 , P TH Coates 1 2 3
  1. School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
  2. Renal and Transplantation Immunobiology Laboratory, The Royal Adelaide Hospital, Adelaide, South Australia, Australia
  3. Australian Islet Transplant Consortium, Adelaide, Australia
  4. Department of Human Physiology, School of Medicine, Flinders University, Adelaide, South Australia, Australia

Aims: The early loss of functional islet mass (50-70%) due to apoptosis following clinical transplantation contributes to islet allograft failure. Genetic modification of islets with anti-apoptotic genes, such as Insulin-like Growth Factor-II (IGF-II) offers a novel strategy to address this problem. Methods: Rat islets were transduced with Adenoviral (Ad)-IGF-II (MOI 100) for 48 h. Islet cell viability was examined with 7-AAD by flow cytometry and function with a glucose stimulated insulin secretion assay. Ad-IGF-II transduced islets were treated with cytokines (35ng/ml IL-1? and 40ng/ml IFN-?) for 24 h to induce apoptosis. Apoptosis in Ad-IGF-II islets was determined by Annexin V/Propidium Iodide flow cytometry and TUNEL staining. Diabetic NOD-SCID mice received a marginal mass islet graft under the kidney capsule of either Ad-IGF-II (n=13), Ad-GFP (n=13) or untransduced islets (n=13) and were followed for diabetes cure. Results: Ad-IGF-II transduction did not affect islet viability or function. Ad-IGF-II transduced islets constitutively secreted 14.3