Rivas-Carrillo Jorge David, Navarro-Alvarez Nalu, Soto-Gutierrez Alejandro, Okitsu Teru, Chen Yong, Tabata Yasuhiko, Misawa Haruo, Noguchi Hirofumi, Matsumoto Shinichi, Tanaka Noriaki, Kobayashi Naoya
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Cell Transplant. 2006;15(10):939-44. doi: 10.3727/000000006783981323.
Fibroblast growth factor (FGF)-2 has been recognized to be a key element involved in angiogenesis and a putative factor involved in stem cell-mediated islet regeneration. However, the usefulness of FGF-2 in an islet transplantation setting has not yet been explored. We therefore evaluated the effect of FGF-2 on both islet culture and islet transplantation. Isolated islets were cultured in the presence of 100 ng/ml FGF-2 for a week and then the glucose-responding insulin secretion and insulin contents were measured. Gelatinized FGF-2 (100 ng), which allowed the controlled release of FGF-2, was used for islet transplantation of streptozotocin-induced diabetic mice. Islets (150 IEQ), obtained from a single donor, mixed with gelatinized FGF-2, were transplanted into the subrenal capsule of the mice and the animals were observed for 30 days. Revascularization around the islet grafts was examined. The blood glucose levels were measured and the intraperitoneal glucose tolerance test (IPGTT) was performed. The supplementation of FGF-2 maintained proper insulin secretion and insulin contents in an in vitro culture. The use of gelatinized FGF-2 facilitated revascularization and favorable islet engraftment, thus resulting in an amelioration of the blood glucose levels in diabetic mice. The utilization of FGF-2 showed increased contents of insulin in the islet grafts and revealed a similar pattern as that of normal healthy mice in IPGTT. In contrast, the transplantation of islets without FGF-2 supplementation showed poor revascularization and failed to control the blood glucose levels in the diabetic mice.
成纤维细胞生长因子（FGF）-2已被认为是参与血管生成的关键因素以及参与干细胞介导的胰岛再生的一个假定因子。然而，FGF-2在胰岛移植环境中的效用尚未得到探索。因此，我们评估了FGF-2对胰岛培养和胰岛移植的影响。将分离的胰岛在100 ng/ml FGF-2存在的情况下培养一周，然后测量葡萄糖反应性胰岛素分泌和胰岛素含量。允许FGF-2控释的凝胶化FGF-2（100 ng）用于链脲佐菌素诱导的糖尿病小鼠的胰岛移植。将从单个供体获得的胰岛（150个胰岛等效物）与凝胶化FGF-2混合，移植到小鼠的肾被膜下，并观察动物30天。检查胰岛移植物周围的血管再生情况。测量血糖水平并进行腹腔葡萄糖耐量试验（IPGTT）。在体外培养中补充FGF-2可维持适当的胰岛素分泌和胰岛素含量。使用凝胶化FGF-2促进了血管再生和良好的胰岛植入，从而改善了糖尿病小鼠的血糖水平。使用FGF-2显示胰岛移植物中胰岛素含量增加，并且在IPGTT中显示出与正常健康小鼠相似的模式。相比之下，未补充FGF-2的胰岛移植显示血管再生不良，并且未能控制糖尿病小鼠的血糖水平。
