Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel.
Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel.
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DOI：
10.1016/j.biomaterials.2012.06.015
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发表时间：
2012-10
期刊：
影响因子：
14
通讯作者：
Fontaine, Magali J.
中科院分区：
文献类型：
--
作者：
Davis, Nicolynn E.;Beenken-Rothkopf, Liese N.;Mirsoian, Annie;Kojic, Nikola;Kaplan, David L.;Barron, Annelise E.;Fontaine, Magali J.
由于胰岛功能和细胞死亡的丧失，生物合成材料内的胰岛封装取得了有限的临床成功。作为替代封装材料，开发了一种基于丝绸的支架，以重新建立在细胞分离过程中损失的胰岛微环境。胰岛用ECM蛋白（层粘连蛋白和胶原蛋白IV）和间充质基质细胞（MSC）封装，已知具有免疫调节特性或增强胰岛细胞移植的存活和功能。经过7天的体外封装后，胰岛仍然可行并保持胰岛素分泌，以响应葡萄糖刺激。用胶原蛋白IV封装的胰岛分别在第2天和第7天分别增加了胰岛素分泌。当胰岛与MSC和ECM蛋白共封存时，观察到胰岛胰岛素分泌的3.2倍协同改善。此外，封装的胰岛具有功能基因的基因表达增加。与未封装的细胞相比，胰岛素I I，胰岛素II，胰高血糖素，生长抑素和PDX-1，以及脱二差基因Cytokeratin 19和Vimentin的表达较低。这项工作表明，用MSC和ECM蛋白封装在丝绸中增强了胰岛功能，并且随着进一步的发展，可能具有在体内胰岛输送的合适平台。
Pancreatic islet encapsulation within biosynthetic materials has had limited clinical success due to loss of islet function and cell death. As an alternative encapsulation material, a silk-based scaffold was developed to reestablish the islet microenvironment lost during cell isolation. Islets were encapsulated with ECM proteins (laminin and collagen IV) and mesenchymal stromal cells (MSCs), known to have immunomodulatory properties or to enhance islet cell graft survival and function. After a 7 day in vitro encapsulation, islets remained viable and maintained insulin secretion in response to glucose stimulation. Islets encapsulated with collagen IV, or laminin had increased insulin secretion at day 2 and day 7, respectively. A 3.2-fold synergistic improvement in islet insulin secretion was observed when islets were co-encapsulated with MSCs and ECM proteins. Furthermore, encapsulated islets had increased gene expression of functional genes; insulin I, insulin II, glucagon, somatostatin, and PDX-1, and lower expression of the de-differentiation genes cytokeratin 19 and vimentin compared to non-encapsulated cells. This work demonstrates that encapsulation in silk with both MSCs and ECM proteins enhances islet function and with further development may have potential as a suitable platform for islet delivery in vivo.
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