Krishnan Laxminarayanan, Touroo Jeremy, Reed Robert, Boland Eugene, Hoying James B, Williams Stuart K
Cardiovascular Innovation Institute, University of Louisville and Jewish Hospital, Louisville, Kentucky, 40202.
J Biomed Mater Res A. 2014 Jul;102(7):2208-19. doi: 10.1002/jbm.a.34900. Epub 2013 Aug 10.
A clinical need exists for a cell delivery device that supports long-term cell viability, cell retention within the device and retrieval of delivered cells if necessary. Previously, cell isolation devices have been based on hollow fiber membranes, porous polymer scaffolds, alginate systems, or micro-machined membranes. We present the development and characterization of a novel dual porosity electrospun membrane based device, which supports cellular infiltration and vascularization of its outer porous layer and maintains cellular isolation within a lumen bounded by an inner low porosity layer. Electrospinning conditions were initially established to support electrospun fiber deposition onto nonconductive silicone surfaces. With these parameters established, devices for in vivo evaluations were produced using nylon as a nonconductive scaffold for deposition of dual porosity electrospun fibers. The outer porous layer supported the development of a penetrating microcirculation and the membrane supported the transfer of insulin from encapsulated sustained release pellets for 4 weeks. Viable cells implanted within the device could be identified after 2 weeks of implantation. Through the successful demonstration of survival and cellular isolation of human epithelial cells within the implanted devices and the ability to use the device to deliver insulin, we have established the utility of this device toward localized cell transplantation. The cell delivery device establishes a platform to test the feasibility of approaches to cell dose control and cell localization at the site of implantation in the clinical use of modified autologous or allogeneic cells.
临床上需要一种能够支持细胞长期存活、细胞在装置内保留以及在必要时取回所输送细胞的细胞输送装置。以前,细胞隔离装置基于中空纤维膜、多孔聚合物支架、藻酸盐系统或微加工膜。我们展示了一种新型双孔隙率电纺膜基装置的开发与表征,该装置支持其外部多孔层的细胞浸润和血管化,并在由内部低孔隙率层界定的管腔内维持细胞隔离。最初确定了电纺条件以支持电纺纤维沉积到非导电硅胶表面上。确定这些参数后,使用尼龙作为非导电支架来生产用于体内评估的装置,以沉积双孔隙率电纺纤维。外部多孔层支持穿透性微循环的发展,并且该膜支持胰岛素从包封的缓释微丸中转移达4周。植入2周后可以识别植入装置内的活细胞。通过成功证明植入装置内人上皮细胞的存活和细胞隔离以及使用该装置输送胰岛素的能力,我们确立了该装置在局部细胞移植方面的实用性。该细胞输送装置建立了一个平台,用于测试在临床使用改良自体或同种异体细胞时控制细胞剂量和将细胞定位在植入部位的方法的可行性。