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Endothelialized collagen based pseudo-islets enables tuneable subcutaneous diabetes therapy.
Biomaterials ( IF 12.8 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.biomaterials.2019.119710
Alexander E Vlahos 1 , Sean M Kinney 2 , Benjamin R Kingston 1 , Sara Keshavjee 1 , So-Yoon Won 1 , Anastasiya Martyts 1 , Warren C W Chan 3 , Michael V Sefton 2
Affiliation  

Pancreatic islets are fragile cell clusters and many isolated islets are not suitable for transplantation. Furthermore, following transplantation, islets will experience a state of hypoxia and poor nutrient diffusion before revascularization, which is detrimental to islet survival; this is affected by islet size and health. Here we engineered tuneable size-controlled pseudo-islets created by dispersing de-aggregated islets in an endothelialized collagen scaffold. This supported subcutaneous engraftment, which returned streptozotocin-induced diabetic mice to normoglycemia. Whole-implant imaging after tissue clearing demonstrated pseudo-islets regenerated their vascular architecture and insulin-secreting β-cells were within 5 μm of a perfusable vessel - a feature unique to this approach. By using an endothelialized collagen scaffold, this work highlights a novel "bottom-up" approach to islet engineering that provides control over the size and composition of the constructs, while enabling the critical ability to revascularize and engraft when transplanted into the clinically useful subcutaneous space.

中文翻译:

基于内皮化胶原蛋白的假胰岛能够进行可调节的皮下糖尿病治疗。

胰岛是易碎的细胞簇,许多分离的胰岛不适合移植。此外,在移植后,胰岛将在血运重建之前经历缺氧和营养物质扩散不良的状态,这对胰岛的存活是有害的。这受胰岛大小和健康状况的影响。在这里,我们设计了通过将解聚的胰岛分散在内皮化的胶原蛋白支架中而创建的可调大小控制的伪胰岛。这支持皮下植入,这使链脲佐菌素诱导的糖尿病小鼠恢复正常血糖。组织清除后的全植入物成像显示假胰岛可再生其血管结构,而分泌胰岛素的β细胞在可灌注血管的5μm以内-这是该方法独有的功能。通过使用内皮化的胶原蛋白支架,
更新日期:2019-12-27
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