Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas
Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas
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DOI：
10.3727/096368912x657341
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Rotem, Avi
中科院分区：
文献类型：
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作者：
Barkai, Uriel;Weir, Gordon C.;Rotem, Avi
当前糖尿病的流行及其对我们医疗保健系统的巨大负担需要更好的治疗策略。在这里，我们提出了一种有希望的治疗策略的新方法，可能适用于所有胰岛素依赖型糖尿病患者。我们设计了一种皮下植入式生物人工胰腺(BAP)-“β -空气”，能够克服当前临床胰岛移植方案中的关键挑战：为移植物提供充足的氧气和保护供体胰岛免受宿主免疫系统的攻击。该系统由固定在海藻酸盐水凝胶中的朗格汉斯胰岛、毒气室、透气膜、外膜和机械支架组成。该微创植入式装置通过皮下植入的通路口充氧，使链脲霉素诱导的糖尿病大鼠血糖控制指标（静脉葡萄糖耐量试验和糖化血红蛋白）完全正常化长达6个月。设备的功能依赖于设备的氧气供应，因为当氧气供应停止时移植物失效。此外，我们发现该装置具有免疫保护作用，因为它不仅允许同种移植物存活，也允许同种移植物存活。移植装置的组织学检查显示形态和功能完整的胰岛；周围组织无炎症征象，在植入部位可见血管。胰岛负荷密度的进一步增加将证明将该系统转化为临床试验是合理的，为糖尿病治疗的新方法开辟了潜力。
The current epidemic of diabetes with its overwhelming burden on our healthcare system requires better therapeutic strategies. Here we present a promising novel approach for a curative strategy that may be accessible for all insulin-dependent diabetes patients. We designed a subcutaneous implantable bioartificial pancreas (BAP)-the "beta-Air" that is able to overcome critical challenges in current clinical islet transplantation protocols: adequate oxygen supply to the graft and protection of donor islets against the host immune system. The system consists of islets of Langerhans immobilized in an alginate hydrogel, a gas chamber, a gas permeable membrane, an external membrane, and a mechanical support. The minimally invasive implantable device, refueled with oxygen via subdermally implanted access ports, completely normalized diabetic indicators of glycemic control (blood glucose intravenous glucose tolerance test and HbA1c) in streptozotocin-induced diabetic rats for periods up to 6 months. The functionality of the device was dependent on oxygen supply to the device as the grafts failed when oxygen supply was ceased. In addition, we showed that the device is immuno-protective as it allowed for survival of not only isografts but also of allografts. Histological examination of the explanted devices demonstrated morphologically and functionally intact islets; the surrounding tissue was without signs of inflammation and showed visual evidence of vasculature at the site of implantation. Further increase in islets loading density will justify the translation of the system to clinical trials, opening up the potential for a novel approach in diabetes therapy.