Dufour Jannette M, Rajotte Ray V, Zimmerman Mark, Rezania Alireza, Kin Tatsuya, Dixon Doreen E, Korbutt Gregory S
Surgical-Medical Research Institute, University of Alberta, Edmonton, AB, Canada.
Tissue Eng. 2005 Sep-Oct;11(9-10):1323-31. doi: 10.1089/ten.2005.11.1323.
Clinical islet transplantation in liver has achieved normoglycemia. However, this site may not be ideal for islet survival. To create a more optimal site for islet transplantation, we have developed a construct with biodegradable scaffolds. Islets were seeded in scaffolds and transplanted into the epididymal fat pad of diabetic BALB/c mice. Controls included islets transplanted underneath the kidney capsule or into the fat pad without scaffolds. All animals with islets in scaffolds or the kidney became normoglycemic and maintained this metabolic state. When islets were transplanted without scaffolds the time to achieve normoglycemia was significantly increased and less than 45% of mice survived. An oral glucose tolerance test was performed on the scaffold and kidney groups with similar blood glucose levels and area under the curve values between the groups. Grafts were removed at more than 100 days posttransplantation and all animals became hyperglycemic. There was no significant difference in insulin content between the grafts and all grafts were well vascularized with insulin-positive beta cells. Therefore, islets in scaffolds function and restore diabetic animals to normoglycemic levels, similar to islets transplanted underneath the kidney capsule, suggesting scaffolds can be used to create a site for islet transplantation.
肝脏中的临床胰岛移植已实现血糖正常。然而，该部位可能并非胰岛存活的理想场所。为了创建一个更适合胰岛移植的部位，我们开发了一种带有可生物降解支架的构建物。将胰岛接种到支架中，并移植到糖尿病BALB/c小鼠的附睾脂肪垫中。对照组包括移植到肾包膜下或无支架的脂肪垫中的胰岛。所有植入支架或肾脏中的胰岛的动物均实现血糖正常，并维持这种代谢状态。当无支架移植胰岛时，达到血糖正常的时间显著延长，且存活的小鼠不到45%。对血糖水平相似且组间曲线下面积值相近的支架组和肾脏组进行了口服葡萄糖耐量试验。移植后100多天取出移植物，所有动物均出现高血糖。移植物之间的胰岛素含量无显著差异，所有移植物均有良好的血管化，且含有胰岛素阳性的β细胞。因此，支架中的胰岛发挥功能并使糖尿病动物恢复到血糖正常水平，类似于移植到肾包膜下的胰岛，这表明支架可用于创建胰岛移植部位。
