Baylor All Saints Medical Center, Baylor Research Institute, Fort Worth, TX, USA.
Cell Transplant. 2012;21(2-3):517-23. doi: 10.3727/096368911X605439.
For clinical islet transplantation, isolated islets deteriorate rapidly in culture, although culturing islets prior to transplantation provides flexibility for evaluation of isolated islets and pretreatment of patients. In the present study, we compared human fresh islets to cultured islets with in vitro and in vivo assays. After culture for 24, 48, and 72 h, islet yield significantly decreased from 2,000 to 1,738 ± 26 (13% loss), 1,525 ± 30 (24% loss), or 1,298 ± 18 IEQ (35% loss), respectively. The ATP contents were significantly higher in the 6-h cultured group (near fresh group) than in 48-h culture groups. The stimulation index was relatively higher in the 6-h cultured group than in 48-h cultured group. Human islets with or without culture were transplanted into diabetic nude mice. The attainability of posttransplantation normoglycemia was significantly higher in fresh group than in the culture groups. Intraperitoneal glucose tolerance testing (IPGTT) showed that the blood glucose levels of mice transplanted with fresh islets were significantly lower than with cultured islets at 30, 60, 90, and 120 min after injection. These data suggest that human islet transplantation without culture could avoid the deterioration of islets during culture and improve the outcome of islet transplantation. Based on these data, we have transplanted fresh islets without culture for our current clinical islet transplantation protocol.
对于临床胰岛移植,分离的胰岛在培养中迅速恶化,尽管在移植前培养胰岛为分离胰岛的评估和患者的预处理提供了灵活性。在本研究中,我们比较了新鲜人胰岛与体外和体内检测的培养胰岛。培养 24、48 和 72 h 后,胰岛产量分别显著从 2000 个降至 1738 ± 26(13%损失)、1525 ± 30(24%损失)或 1298 ± 18 IEQ(35%损失)。培养 6 h 组的 ATP 含量明显高于培养 48 h 组。培养 6 h 组的刺激指数相对高于培养 48 h 组。将有或无培养的人胰岛移植到糖尿病裸鼠中。与培养组相比,新鲜胰岛移植后达到移植后正常血糖的可能性明显更高。腹腔葡萄糖耐量试验(IPGTT)显示,移植新鲜胰岛的小鼠在注射后 30、60、90 和 120 min 时的血糖水平明显低于移植培养胰岛的小鼠。这些数据表明,人胰岛移植无需培养可避免胰岛在培养过程中的恶化,改善胰岛移植的效果。基于这些数据,我们已经在我们目前的临床胰岛移植方案中移植了未经培养的新鲜胰岛。