Shahbazov Rauf, Kanak Mazhar A, Takita Morihito, Kunnathodi Faisal, Khan Omar, Borenstein Nofit, Lawrence Michael C, Levy Marlon F, Naziruddin Bashoo
Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
The Institute of Biomedical Studies, Baylor University, Waco, TX, USA.
Diabetes Metab Res Rev. 2016 Mar;32(3):268-77. doi: 10.1002/dmrr.2714. Epub 2015 Oct 28.
The pancreatic islet damage that occurs through an inflammatory response and hypoxia after infusion is a major hurdle in islet transplantation. Because essential phospholipids (EPL) have been shown to exhibit anti-inflammatory properties in liver disease, we analysed their protective effect on islets in inflammatory or hypoxic conditions.
We evaluated the viability of mouse and human islets cultured with cytokines or in hypoxic conditions for 48 h and measured cytokine expression in islets by quantitative polymerase chain reaction. We then employed an in vivo mouse assay, transplanting a marginal dose of human islets treated with or without EPL into the subcapsule of the kidney in diabetic nude mice and determining the cure rate.
The viability of mouse and human islets damaged by cytokines was significantly improved by supplementation of EPL in the culture (p = 0.003 and <0.001 for mouse and human islets respectively). EPL significantly inhibited intracellular expression of IL-1β and IL-6 in cytokine-damaged human islets (p < 0.001). The viability of human islets in hypoxic conditions was significantly better when treated with EPL (p < 0.001). In the in vivo mouse assay, the EPL-treated islet group had a higher cure rate than the untreated control, with marginal statistical significance (75 and 17% respectively, p = 0.07).
EPL could be a potent agent to protect islets from inflammatory and hypoxic conditions after isolation procedures. Further studies to clarify the effect of EPL in islet transplantation are warranted.
输注后通过炎症反应和缺氧发生的胰岛损伤是胰岛移植的主要障碍。由于必需磷脂(EPL)已被证明在肝病中具有抗炎特性,我们分析了它们在炎症或缺氧条件下对胰岛的保护作用。
我们评估了在细胞因子作用下或缺氧条件下培养48小时的小鼠和人类胰岛的活力,并通过定量聚合酶链反应测量胰岛中的细胞因子表达。然后我们进行了一项体内小鼠试验,将经或未经EPL处理的边缘剂量人类胰岛移植到糖尿病裸鼠的肾被膜下,并确定治愈率。
通过在培养物中补充EPL,细胞因子损伤的小鼠和人类胰岛的活力得到显著改善(小鼠和人类胰岛分别为p = 0.003和<0.001)。EPL显著抑制细胞因子损伤的人类胰岛中IL-1β和IL-6的细胞内表达(p < 0.001)。用EPL处理时,缺氧条件下人类胰岛的活力明显更好(p < 0.001)。在体内小鼠试验中,EPL处理的胰岛组的治愈率高于未处理的对照组,具有边缘统计学意义(分别为75%和17%,p = 0.07)。
EPL可能是一种有效的试剂,可在分离程序后保护胰岛免受炎症和缺氧条件的影响。有必要进行进一步研究以阐明EPL在胰岛移植中的作用。