Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial.
Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial.
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DOI：
10.1016/j.biomaterials.2017.03.018
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发表时间：
2017-06
期刊：
影响因子：
14
通讯作者：
Stabler CL
中科院分区：
文献类型：
--
作者：
Coronel MM;Geusz R;Stabler CL
组织工程移植存活和疗效的主要障碍是氧合不足，因此不支持的氧张力导致植入物内显著的细胞功能障碍和死亡。在之前的报告中，我们开发了一种创新的生氧生物材料，称为OxySite，为细胞提供原位氧合支持，防止缺氧引起的损伤。在此，我们探索了这种生物材料通过减少细胞死亡、支持代谢活动、维持有氧代谢、保持葡萄糖反应性和减少炎症细胞因子的产生来减轻大鼠和非人灵长类动物胰岛缺氧应激的能力。此外，通过将先前与OxySite共培养的胰岛移植到糖尿病大鼠模型中，研究了补充氧合对体内细胞功能的影响。移植结果显示，当在肝外部位移植时，经氧酶处理的胰岛的移植物疗效显著改善。这些结果证明了OxySite材料在培养过程中减轻胰岛中有害的缺氧诱导通路的激活的有效性，并强调了原位氧合对胰岛移植结果的重要性。
A major obstacle in the survival and efficacy of tissue engineered transplants is inadequate oxygenation, whereby unsupportive oxygen tensions result in significant cellular dysfunction and death within the implant. In a previous report, we developed an innovative oxygen generating biomaterial, termed OxySite, to provide supportive in situ oxygenation to cells and prevent hypoxia-induced damage. Herein, we explored the capacity of this biomaterial to mitigate hypoxic stress in both rat and nonhuman primate pancreatic islets by decreasing cell death, supporting metabolic activity, sustaining aerobic metabolism, preserving glucose responsiveness, and decreasing the generation of inflammatory cytokines. Further, the impact of supplemental oxygenation on in vivo cell function was explored by the transplantation of islets previously co-cultured with OxySite into a diabetic rat model. Transplant outcomes revealed significant improvement in graft efficacy for OxySite-treated islets, when transplanted within an extrahepatic site. These results demonstrate the potency of the OxySite material to mitigate activation of detrimental hypoxia-induced pathways in islets during culture and highlights the importance of in situ oxygenation on resulting islet transplant outcomes.