Drug carrier systems based on collagen-alginate composite structures for improving the performance of GDNF-secreting HEK293 cells
Drug carrier systems based on collagen-alginate composite structures for improving the performance of GDNF-secreting HEK293 cells
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DOI：
10.1016/j.biomaterials.2008.11.017
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发表时间：
2009-02-01
期刊：
影响因子：
14
通讯作者：
Chan, B. P.
中科院分区：
文献类型：
--
作者：
Lee, M.;Lo, A. C.;Chan, B. P.
胶质细胞源性神经营养因子（GDNF）是一种有效的神经营养因子。开发促进 GDNF 控释的药物递送技术对于应用 GDNF 治疗神经退行性疾病至关重要。我们之前开发了 3D 胶原微球，并证明封装 HEK293 细胞后 GDNF 分泌增强，HEK293 细胞在这些微球中转导过度表达 GDNF。然而，捕获的 HEK293 细胞能够从胶原微球中迁移出来，使其不适合临床应用。在本报告中，我们研究了两种新的载体设计，即胶原蛋白-海藻酸盐复合凝胶和嵌入海藻酸盐凝胶中的胶原微球，以防止HEK293细胞中的细胞渗漏、维持细胞生长和控制GDNF分泌。我们证明，在两种设计中包含藻酸盐凝胶可有效防止细胞渗漏到周围，同时允许 GDNF 分泌，尽管细胞生长速率以藻酸盐浓度依赖性方式降低。两种设计中 GDNF 分泌的差异模式得到了证明。胶原蛋白-海藻酸盐复合凝胶随着时间的推移保持或多或少恒定的GDNF分泌，而嵌入藻酸盐凝胶中的胶原微球随着时间的推移继续增加GDNF的分泌水平。这项研究有助于开发基于细胞的 GDNF 递送装置，用于未来神经退行性疾病的治疗。 (C) 2008 Elsevier Ltd. 保留所有权利。
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor. Development of drug delivery technologies facilitating controlled release of GDNF is critical to applying GDNF in treating neurodegenerative diseases. We previously developed 3D collagen microspheres and demonstrated enhanced GDNF secretion after encapsulation of HEK293 cells, which were transduced to overexpress GDNF in these microspheres. However, the entrapped HEK293 cells were able to migrate out of the collagen microspheres, making it undesirable for clinical applications. In this report, we investigate two new carrier designs, namely collagen-alginate composite gel and collagen microspheres embedded in alginate gel in preventing cell leakage, maintaining cell growth and controlling GDNF secretion in the HEK293 cells. We demonstrated that inclusion of alginate gel in both designs is efficient in preventing cell leakage to the surrounding yet permitting the GDNF secretion, although the cellular growth rate is reduced in an alginate concentration dependent manner. Differential patterns of GDNF secretion in the two designs were demonstrated. The collagen-alginate composite gel maintains a more or less constant GDNF secretion over time while the collagen rnicrospheres embedded in alginate gel continue to increase the secretion level of GDNF over time. This study contributes towards the development of cell-based GDNF delivery devices for the future therapeutics of neurodegenerative diseases. (C) 2008 Elsevier Ltd. All rights reserved.