Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.
Diabetes Metab Res Rev. 2012 Sep;28(6):475-84. doi: 10.1002/dmrr.2294.
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.
缺氧被认为是细胞适应环境应激的关键因素。胰岛移植,特别是免疫隔离胰岛,会中断血管连接,导致胰岛细胞的氧气和营养供应大大减少。已知产生胰岛素的胰腺β细胞对缺氧非常敏感。这种对缺氧的敏感性被认为是移植后β细胞死亡的主要原因之一。已经开发了多种策略来保护β细胞免受缺氧损伤,并向移植的胰岛输送氧气。通过使用基因转染、药物补充、与干细胞共培养和细胞选择等各种技术,可以增强β细胞对缺氧的防御能力。向移植胰岛输送氧气的技术包括皮下部位的局部新血管生成、电化学和光合氧气生成、生物人工胰腺的氧气再填充以及使用高压治疗进行全身氧合。胰岛移植氧气技术领域的进展需要采用多学科方法来探索和优化生物系统成分与不同技术过程之间的相互作用。本文主要关注最近开发的氧合和缺氧损伤保护策略,以实现移植胰岛的糖尿病患者的稳定和长期正常血糖水平。