Mei Lin, Sun Hong-fan, Tang Li-na, Yang Jing, Chang Jin, Song Cun-xian
Tianjin Biomedical Material Key Laboratory, Institute of Biomedical Engineering, CAMS and PUMC, Tianjin 300192, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005 Apr;27(2):190-3.
To explore the possibility of using an endovascular microcoil as a gene delivery system.
Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of platinum microcoil. These antibodies were used to tether adenovirus encoding green fluorescent protein (Ad-GFP). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution.
In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface. After 7 days, GFP was detected on the harvested platinum coil and in the organizing thrombus within the CCA according to fluorescence microscopy and immunohistochemistry. Morphometric analyses revealed that (13.3 +/- 2.0)% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney.
Gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.
探讨使用血管内微线圈作为基因递送系统的可能性。
将抗腺病毒单克隆抗体共价连接到铂微线圈的胶原包被表面。这些抗体用于连接编码绿色荧光蛋白的腺病毒(Ad-GFP)。用大鼠动脉平滑肌细胞(A10)进行细胞培养研究,评估线圈上或其附近的转导情况。将包被有Ad-GFP的铂线圈植入成年大鼠结扎的颈总动脉(CCA)中,建立动脉淤滞和加压模型。7天后,收获CCA节段,取出线圈进行组织病理学和GFP表达研究,同时通过聚合酶链反应评估器官以确定病毒的生物分布。
在细胞培养研究中,仅在铂线圈表面检测到GFP阳性平滑肌细胞。7天后,根据荧光显微镜检查和免疫组织化学,在收获的铂线圈上以及CCA内正在形成的血栓中检测到GFP。形态计量分析显示,通过基因递送系统,在正在形成的血栓中(13.3±2.0)%的细胞被Ad-GFP转导。在肺、肝或肾中通过聚合酶链反应未检测到Ad-GFP。
基因递送血管内微线圈代表了一种基于介入装置的基因治疗系统,可作为单基因或多基因治疗载体的合适平台。