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首页> 外文期刊>Journal of Microencapsulation: Microcapsules Liposomes Nanoparticles Microcells Microspheres >In vivo perivascular implantation of encapsulated packaging cells for prolonged retroviral gene transfer
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In vivo perivascular implantation of encapsulated packaging cells for prolonged retroviral gene transfer

机译：封装的包装细胞在体内血管周围植入，以延长逆转录病毒基因转移

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Long-term benefits of coronary angioplasty rem1lin limited by .rthe treatment- induced renarrowing of arteries, termed restenosis. One of the mechanisms leading to restenosis is the proliferation of smooth muscle cells. Therefore, proliferating cells of the injured arterial wall, which can be selectively transduced by retroviruses, are potential targets for gOOe therapy strategies. A direct single-dose therapeutic application of retrovilral vectors for inhibiti.oIJ;~f cell proliferation is normally limited by too low transduction effilrncies. Encapsulated retrovirus-producing cells release viral vectors from microcap- sules, and may enhance the transduction efficiency by prolonged infection. Primary and immortal murine and porcine cells and murine retrovirus- producing cells were encapsulated 'in cellulose sulphate. Cell viability was monitored by analysing cell metabolism. Safety , stability, transfer efficiency and extent of restenosis usingcapsule~ were determined in a porcine restenosis model for local gene therapy using morphometry, histology, in situ beta- galactosidase assay and PCR. Encapsulation of cells did not impair cell viability. Capsules containing retrovirus-producing cells expressing the (J-galactosidase reporter gene were implanted into periarterial tissue or a pig model of rest- enosis. Three weeks following implantation, (J-galactosidase activity was detected in the pericapsular tissue with a transduction efficiency of"" 1 in 500 cells. Adventitial implantation of vector-producing encapsulated cells for gene therapy may, therefore, facilitate successful targeting of proliferating vascular smooth muscle cells, and allow stable integration of therapeutic genes into surrounding cells. The encapsulation of vector-producing cells could represent a novel and feasible way to optimize local retroviral gene therapy.
机译：冠状动脉成形术rem1lin的长期益处受到治疗引起的血管再狭窄的限制，称为再狭窄。导致再狭窄的机制之一是平滑肌细胞的增殖。因此，可以通过逆转录病毒选择性转导的损伤的动脉壁的增殖细胞是gOOe治疗策略的潜在靶标。后壁载体用于抑制细胞增殖的直接单剂量治疗应用通常受到过低的转导效率的限制。封装的产生逆转录病毒的细胞从微囊中释放病毒载体，并可能通过长期感染而提高转导效率。将原代和永生的鼠和猪细胞以及产生鼠逆转录病毒的细胞封装在硫酸纤维素中。通过分析细胞代谢监测细胞活力。在猪再狭窄模型中使用形态测定法，组织学，原位β-半乳糖苷酶测定法和PCR在用于局部基因治疗的猪再狭窄模型中确定了使用胶囊的再狭窄的安全性，稳定性，转移效率和程度。细胞的包囊不损害细胞活力。将含有表达（J-半乳糖苷酶报告基因的逆转录病毒产生细胞的胶囊）植入动脉周围组织或再狭窄的猪模型中。植入后三周，（在囊周组织中检测到（J-半乳糖苷酶活性的转导效率为“ “每500个细胞中就有1个。因此，将载体产生的封装细胞进行基因疗法的前瞻性植入可能有助于成功靶向增殖的血管平滑肌细胞，并使治疗基因稳定整合到周围细胞中。载体产生细胞的封装可以代表了一种优化本地逆转录病毒基因治疗的新颖可行的方法。

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