Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets.
Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets.
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DOI：
10.1016/j.biomaterials.2010.04.002
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发表时间：
2010-08
期刊：
影响因子：
14
通讯作者：
Stupp, Samuel I.
中科院分区：
文献类型：
--
作者：
Chow, Lesley W.;Wang, Ling-jia;Kaufman, Dixon B.;Stupp, Samuel I.
纳米级细丝的超分子自组装为在诸如胰岛等密集细胞聚集体内给细胞传递信号提供了一种载体。我们先前开发了一种肝素结合肽两亲物（HBPA），当它与肝素混合时，在重量百分比为1%的浓度下可自组装成纳米纤维凝胶，并激活肝素结合的血管生成生长因子。在此我们报道了使用浓度低100倍的这些分子来促使纳米纤维进入密集的胰岛内部。利用荧光标记物，显示HBPA分子、肝素和FGF2存在于小鼠胰岛内部及其表面。发现胰岛内的纳米纤维对于将FGF2在胰岛内保留48小时以及在培养至少7天内显著提高细胞活力是必需的。此外，在培养3天内观察到纳米纤维可增强胰岛素分泌。与HBPA/肝素纳米纤维一起递送FGF2和VEGF还诱导了大量胰岛内皮细胞从胰岛向肽两亲物三维基质中出芽。我们认为生物活性纳米纤维作为一种人工细胞外基质渗透到胰岛内部能够在体外提高细胞活力和功能，并在存在诸如FGF2和VEGF等生长因子的情况下增强其血管化。此处所描述的方法可能对胰岛移植治疗1型糖尿病具有重大影响。
Supramolecular self-assembly of nanoscale filaments offers a vehicle to signal cells within dense cell aggregates such as pancreatic islets. We previously developed a heparin-binding peptide amphiphile (HBPA) that self-assembles into nanofiber gels at concentrations of 1% by weight when mixed with heparin and activates heparin-binding, angiogenic growth factors. We report here on the use of these molecules at concentrations 100 times lower to drive delivery of the nanofibers into the dense islet interior. Using fluorescent markers, HBPA molecules, heparin, and FGF2 were shown to be present in and on the surface of murine islets. The intraislet nanofibers were found to be necessary to retain FGF2 within the islet for 48 hours and to increase cell viability significantly for at least 7 days in culture. Furthermore, enhanced insulin secretion was observed with the nanofibers for 3 days in culture. Delivery of FGF2 and VEGF in conjunction with the HBPA/heparin nanofibers also induced a significant amount of islet endothelial cell sprouting from the islets into a peptide amphiphile 3-D matrix. We believe the infiltration of bioactive nanofibers in the interior of islets as an artificial ECM can improve cell viability and function in vitro and enhance their vascularization in the presence of growth factors such as FGF2 and VEGF. The approach described here may have significant impact on islet transplantation to treat type 1 diabetes.
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影响因子：
14
作者：
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