Zhang Xulang, He Hongyan, Yen Chi, Ho Wiston, Lee L James
NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, 140 West 19th Avenue, Columbus, OH 43210, USA.
Biomaterials. 2008 Nov;29(31):4253-9. doi: 10.1016/j.biomaterials.2008.07.032. Epub 2008 Aug 9.
To demonstrate the transplantation of drug-secreting cells with immunoprotection, a biodegradable delivery device combining two nanoporous capsules is developed using secretory alkaline phosphatase gene (SEAP) transfected mouse embryonic stem (mES) cells as a model system. The outer capsule is a poly (ethylene glycol) (PEG)-coated poly (epsilon-caprolactone) (PCL) chamber covered with a PEG grafted PCL nanoporous membrane made by phase inversion technique. SEAP gene transfected mES cells encapsulated in alginate-poly-L-lysine (AP) microcapsules are placed in the PCL capsule. Both nanoporous capsules showed good immunoprotection in the IgG solution. In microcapsules, mES cells could form a spheroid embryonic body (EB) and grow close to the microcapsule size. The secreted SEAP from encapsulated mES cells increased gradually to a maximum value before reaching a steady level, following the cell growth pattern in the microcapsule. Without microcapsules, mES cells only formed a monolayer in the large PCL capsule. The secreted SEAP release was very low. The integrated device showed a similar cell growth pattern to that in microcapsules alone, while the SEAP release rate could be regulated by the pore size of the large capsule. This integrated device can achieve multi-functionalities for cell-based therapy, i.e. a 3-D microenvironment provided by microcapsules for cell growth, superior immunoprotection and controllable release performance provided by the two nanoporous membranes, and good fibrosis prevention by PEG surface modification of the large capsule.
为了证明具有免疫保护作用的药物分泌细胞的移植，使用分泌性碱性磷酸酶基因（SEAP）转染的小鼠胚胎干细胞（mES）作为模型系统，开发了一种结合两个纳米多孔胶囊的可生物降解递送装置。外胶囊是一个聚（乙二醇）（PEG）涂层的聚（ε-己内酯）（PCL）腔室，上面覆盖着通过相转化技术制成的PEG接枝PCL纳米多孔膜。封装在藻酸盐-聚-L-赖氨酸（AP）微胶囊中的SEAP基因转染的mES细胞被放置在PCL胶囊中。两种纳米多孔胶囊在IgG溶液中均表现出良好的免疫保护作用。在微胶囊中，mES细胞可以形成球形胚体（EB）并生长至接近微胶囊大小。封装的mES细胞分泌的SEAP随着微胶囊中细胞的生长模式逐渐增加至最大值，然后达到稳定水平。没有微胶囊时，mES细胞仅在大的PCL胶囊中形成单层。分泌的SEAP释放量非常低。该集成装置显示出与单独的微胶囊中相似的细胞生长模式，而SEAP的释放速率可以通过大胶囊的孔径来调节。这种集成装置可以实现基于细胞治疗的多功能性，即微胶囊为细胞生长提供三维微环境，两个纳米多孔膜提供卓越的免疫保护和可控释放性能，以及通过大胶囊的PEG表面修饰实现良好的纤维化预防。
