Lee M, Lo A C, Cheung P T, Wong D, Chan B P
Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
Biomaterials. 2009 Feb;30(6):1214-21. doi: 10.1016/j.biomaterials.2008.11.017. Epub 2008 Dec 6.
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 microspheres 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.
胶质细胞系源性神经营养因子（GDNF）是一种强效神经营养因子。开发能够促进GDNF控释的药物递送技术对于将GDNF应用于治疗神经退行性疾病至关重要。我们之前开发了三维胶原蛋白微球，并证明在包裹转导以在这些微球中过表达GDNF的HEK293细胞后，GDNF分泌增加。然而，被包裹的HEK293细胞能够从胶原蛋白微球中迁移出来，这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蛋白微球，以防止细胞泄漏、维持细胞生长并控制HEK293细胞中GDNF的分泌。我们证明，在两种设计中加入海藻酸盐凝胶都能有效地防止细胞泄漏到周围环境中，但允许GDNF分泌，尽管细胞生长速率以海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，而嵌入海藻酸盐凝胶中的胶原蛋白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用于未来神经退行性疾病治疗的基于细胞的GDNF递送装置。
