New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch.

New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch.
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DOI:
10.1016/j.transproceed.2011.10.030
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发表时间:
2011-11
影响因子:
0.9
通讯作者:
Opara, E. C.
Opara, E. C.
中科院分区:
医学4区
文献类型:
--
作者:
McQuilling, J. P.;Arenas-Herrera, J.;Childers, C.;Pareta, R. A.;Khanna, O.;Jiang, B.;Brey, E. M.;Farney, A. C.;Opara, E. C.

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由于缺乏血管供应而导致的严重缺氧以及无法取回移植在腹腔中的包封胰岛进行活检和随后的评估是胰岛移植包封策略临床应用的障碍。我们最近提出了一个网膜袋模型作为替代网站的封装胰岛移植,也描述了一个多层微胶囊系统,适用于共封装的胰岛与血管生成蛋白,其中后者可以封装在外层,以诱导血管化的封装胰岛移植物。本研究的目的是确定从网膜袋移植物中新胶囊系统外层释放的成纤维细胞生长因子(FGF-1)的血管生成功效。我们制备了两组海藻酸盐微球,每组直径约600 μm,两层海藻酸盐之间用半透性聚L-鸟氨酸(PLO)膜隔开。虽然一组微胶囊不含蛋白质(对照),但FGF-1(1.794 μg/100个微胶囊)包封在另一组(测试)的外层中。从2组中的每一组,将100个微囊分别移植到在每只正常刘易斯大鼠中产生的网膜袋中,并在14天后取回,用于使用连续样品切片的技术通过定量三维成像对CD 31染色来分析血管密度。我们发现,从测试微胶囊外层释放的FGF-1诱导的平均± SD血管密度(mm 2)为198.8 ± 59.2,而对照胶囊植入物中测量的袋中的密度为128.9 ± 10.9(P = 0.03; n = 5只动物/组)。我们的结论是,我们的新藻酸盐微胶囊系统的外层是一种有效的药物输送装置,用于增强移植物新生血管在可回收的网膜袋。
Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. We recently proposed an omentum pouch model as an alternative site of encapsulated islet transplantation and have also described a multi-layer microcapsule system suitable for coencapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the angiogenic efficacy of fibroblast growth factor (FGF-1) released from the external layer of the new capsule system in the omentum pouch graft. We prepared 2 groups of alginate microspheres, each measuring ~600 μm in diameter with a semipermeable poly-L-ornithine (PLO) membrane separating 2 alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 μg/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative three-dimensional imaging. We found that FGF-1 released from the external layer of the test microcapsules induced a mean ± SD vessel density (mm2) of 198.8 ± 59.2 compared with a density of 128.9 ± 10.9 in pouches measured in control capsule implants (P = .03; n = 5 animals/group). We concluded that the external layer of our new alginate microcapsule system is an effective drug delivery device for enhancement of graft neovascularization in a retrievable omentum pouch.
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发表时间: 2010-11
影响因子: 4.9
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影响因子: 3
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