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A prevascularized tissue engineering chamber supports growth and function of islets and progenitor cells in diabetic mice

机译：预血管化组织工程腔室支持糖尿病小鼠中胰岛和祖细胞的生长和功能

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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.
机译：最近的研究表明，通过将胰岛移植到血管化的组织工程室中，可以在鼠模型中逆转1型糖尿病。在使用预血管化腔室的初步实验中，我们观察到最初无法正常运转的胰岛移植物在植入后数周可能显示出延迟的功能发作。我们试图表征这种现象。根据链脲佐菌素诱导的糖尿病C57BL / 6J小鼠的上腹部血管，将胰岛移植到血管形成前的组织工程室中。用500个胰岛移植动物，并在移植后1、4、8和16周观察。每周血糖（BG）测量显示，移植后6.8周平均开始维持移植物功能。去除房室后恢复到糖尿病状态证明了移植功能。成熟的移植物显示胰岛组织在组织构建体中聚集在一起。在8周和16周时，胰岛素阳性的内分泌组织染色量与移植物功能相关。然而，在第1和第4周，如通过内分泌染色观察到的，胰岛组织没有明显可见。不论移植物的功能如何，所有胰岛组织均显示密集的血管形成和偶发的交感神经。在早期时间点，在移植物中观察到了针对细胞角蛋白7和-19的免疫阳性细胞，并且已从这些祖细胞中分化出了产生激素的细胞。我们的数据表明，胰管来源的祖细胞在体内仍然可以存活，并在移植后最终分化并成熟为功能性胰岛。我们在腹股沟处的血管形成前的组织工程腔室可在植入后两个月内支持移植组织的成熟和功能。

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