O'Brien Institutem, St. Vincent's Hospital Campus, Melbourne, VIC, Australia.
Islets. 2011 Sep-Oct;3(5):271-83. doi: 10.4161/isl.3.5.15942. Epub 2011 Sep 1.
Recent studies have shown that type 1 diabetes can be reversed in a murine model by islet transplantation to a vascularized tissue engineering chamber. In preliminary experiments using a prevascularized chamber we observed that islet grafts not functioning initially can show a delayed onset of function several weeks after implantation. We sought to characterize this phenomenon. Islets were transplanted into prevascularized tissue engineering chambers based on the epigastric vessels in streptozotocin induced diabetic C57BL/6J mice. Animals were transplanted with 500 islets and observed at 1, 4, 8 and 16 weeks post transplantation. Weekly blood glucose (BG) measurements revealed an average onset of maintained graft function 6.8 weeks post transplantation. Graft function was proven by a return to a diabetic state following chamber removal. Mature grafts showed islet tissue clustered together within the tissue construct. The quantity of endocrine tissue staining positive for insulin correlated with graft function at 8 and 16 weeks. However, at 1 and 4 weeks, islet tissue was not evidently visible as observed by endocrine staining. All islet tissue showed dense vascularization and sporadic sympathetic innervation, irrespective of the graft's function. Immunopositive cells for Cytokeratin-7 and -19 were observed in the grafts at early time points and hormone producing cells appear to have been differentiated from these progenitors. Our data demonstrates that pancreatic duct-derived progenitors remain viable in vivo and eventually differentiate and mature to functional islets following transplantation. Our prevascularized tissue-engineering chamber in the groin supports maturation and function of the grafted tissue by two months after implantation.
最近的研究表明，1 型糖尿病可以在鼠模型中通过胰岛移植到血管化的组织工程室来逆转。在使用预血管化室的初步实验中，我们观察到最初未发挥功能的胰岛移植物在植入后几周内会出现功能延迟。我们试图描述这种现象。将胰岛移植到基于链脲佐菌素诱导的糖尿病 C57BL/6J 小鼠上腹血管的预血管化组织工程室中。将 500 个胰岛移植到动物体内，并在移植后 1、4、8 和 16 周进行观察。每周进行血糖 (BG) 测量，结果显示平均在移植后 6.8 周开始维持移植物功能。通过移除室后恢复糖尿病状态来证明移植物功能。成熟的移植物显示胰岛组织在组织构建中聚集在一起。在 8 周和 16 周时，与胰岛素呈阳性反应的内分泌组织的数量与移植物功能相关。然而，在 1 周和 4 周时，通过内分泌染色观察不到胰岛组织。所有胰岛组织均显示出密集的血管化和散在的交感神经支配，与移植物的功能无关。在早期时间点观察到移植组织中 Cytokeratin-7 和 -19 的免疫阳性细胞，并且激素产生细胞似乎已经从这些祖细胞分化而来。我们的数据表明，胰腺导管衍生的祖细胞在体内仍然存活，并在移植后最终分化和成熟为功能性胰岛。我们在腹股沟的预血管化组织工程室通过两个月的时间支持移植组织的成熟和功能。
