Beltrão-Braga Patricia C B, Koh Ivan H J, Silva Maria R R, Gutierrez Paulo S, Han Sang W
Department of Biophysics, UNIFESP-EPM, São Paulo, Brazil.
Cell Transplant. 2002;11(6):583-92.
Vascular smooth muscle cells (VSMC) are ideal for systemic gene therapy because of their proximity to blood vessels and they have demonstrated long-term exogenous gene expression in vivo. However, the procedure generally followed to seed the transduced VSMC onto arteries denuded of endothelial cells usually induces stenosis and thrombosis, with a consequent high risk for use in humans. We demonstrate here that the vascular adventitia is a suitable place to introduce transduced VSMC and to secrete therapeutic proteins into the blood stream by a simple procedure, avoiding postoperative vascular complications. Transduced VSMC, with the retroviral vectors carrying the human growth hormone gene (hGH), were seeded into the adventitia of the rat abdominal aorta by single injection of a cell suspension. Based on the hGH and anti-hGH production in serum and on histological analysis of the removed aortas, we demonstrated hGH production over the 2-month experimental period. None of the animals used in the experiment showed stenosis, thrombosis, or other vascular or visible physiological abnormalities.
血管平滑肌细胞（VSMC）因其靠近血管，是全身基因治疗的理想选择，并且已证明其能在体内长期表达外源基因。然而，通常将转导的VSMC接种到去除内皮细胞的动脉上的操作通常会引发狭窄和血栓形成，因此在人体应用中存在高风险。我们在此证明，血管外膜是通过简单程序引入转导的VSMC并将治疗性蛋白质分泌到血流中的合适部位，可避免术后血管并发症。携带人生长激素基因（hGH）的逆转录病毒载体转导的VSMC，通过单次注射细胞悬液接种到大鼠腹主动脉外膜。基于血清中hGH和抗hGH的产生以及对取出主动脉的组织学分析，我们证明了在2个月的实验期内有hGH产生。实验中使用的动物均未出现狭窄、血栓形成或其他血管或可见的生理异常。
