Pancreatic islet transplantation has not yet succeeded as an overall treatment for type 1 diabetes because of limited access to donor islets, as well as low efficacy and poor reproducibility of the current procedure. Herein, a method to create islets-like composite clusters (coclusters) from dispersed endocrine cells and supportive cells is described, attempting to improve compatibility with the recipient and more efficiently make use of the donor-derived material. To mimic the extracellular matrix environment, recombinant spider silk functionalized with cell binding motifs are used as 3D support for the coclusters. A cell binding motif derived from fibronectin (FN) was found superior in promoting cell adherence, while a plain RGD-motif incorporated in the repetitive part of the silk protein (2R) increased the mobility and cluster formation of endocrine cells. Self-assembly of a mixture of FN/2R silk is utilized to integrate endocrine cells together with endothelial and mesenchymal cells into islet-like coclusters. Both xenogenic and allogenic versions of these coclusters were found to be viable and were able to respond to dynamic glucose stimulation with insulin release. Moreover, the endothelial cells were found to be colocalized with the endocrine cells, showing that the silk combined with supportive cells may promote vascularization. This method to engineer combined islet-like coclusters allows donor-derived endocrine cells to be surrounded by supportive cells from the recipient, which have the potential to further promote engraftment in the host and considerably reduce risk of rejection.

中文翻译：

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初级内分泌细胞和支持细胞的整合使用功能化的丝绸促进血管形成的胰岛样簇的形成。

胰腺胰岛移植尚未成功作为1型糖尿病的整体治疗方法，因为该方法无法获得供体胰岛，并且目前的治疗方法疗效低，可重复性差。本文中，描述了一种由分散的内分泌细胞和支持细胞创建胰岛样复合簇（簇）的方法，试图改善与受体的相容性并更有效地利用源自供体的材料。为了模仿细胞外基质环境，将具有细胞结合基序功能的重组蜘蛛丝用作3D支持剂。发现源自纤连蛋白（FN）的细胞结合基序在促进细胞黏附方面表现出色，而掺入丝蛋白（2R）重复部分的普通RGD基序增加了内分泌细胞的迁移率和簇形成。利用FN / 2R丝混合物的自组装将内分泌细胞与内皮细胞和间充质细胞整合为胰岛样的簇状细胞。这些coclusters的异种和同种异体版本都被认为是可行的，并且能够通过胰岛素释放对动态葡萄糖刺激作出反应。此外，发现内皮细胞与内分泌细胞共定位，表明丝与支持细胞结合可促进血管形成。这种设计组合的胰岛样簇的方法可以使供体来源的内分泌细胞被受体的支持细胞所包围，