title: Induction of beta-cell resistance to hypoxia and technologies for oxygen delivery to transplanted pancreatic islets.
abstract: Hypoxia is believed to be a crucial factor involved in cell adaptation to environmental stress. Islet transplantation, especially with immunoisolated islets, interrupts vascular connections, resulting in the substantially decreased delivery of oxygen and nutrients to islet cells. Insulin-producing pancreatic beta cells are known to be highly susceptible to oxygen deficiency. Such susceptibility to hypoxia is believed to be one of the main causes of beta-cell death in the post-transplantation period. Different strategies have been developed for the protection of beta cells against hypoxic injury and for oxygen delivery to transplanted islets. The enhancement of beta-cell defense properties against hypoxia has been achieved using various techniques such as gene transfection, drug supplementation, co-culturing with stem cells and cell selection. Technologies for oxygen delivery to transplanted islets include local neovascularization of subcutaneous sites, electrochemical and photosynthetic oxygen generation, oxygen refuelling of bio-artificial pancreas and whole body oxygenation by using hyperbaric therapy. Progress in the field of oxygen technologies for islet transplantation requires a multidisciplinary approach to explore and optimize the interaction between components of the biological system and different technological processes. This review article focuses mainly on the recently developed strategies for oxygenation and protection from hypoxic injury - to achieve stable and long-term normoglycaemia in diabetic patients with transplanted pancreatic islets.
authors.affiliation: Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lazard
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000235:genetics; D002469:Cell Separation; D019254:Genes, bcl-2 / Q000235:genetics; D005818:Genetic Engineering; D052216:Glucagon-Like Peptide 1 / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D019194:Ischemic Preconditioning / Q000379:methods; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology; D008668:Metallothionein / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage; D019397:Pancreas, Artificial; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics; D014810:Vitamin E / Q000627:therapeutic use; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D014810:Vitamin E; D052216:Glucagon-Like Peptide 1; D008668:Metallothionein; D010100:Oxygen