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首页> 外文期刊>Acta Virologica: International Journal >Mesenchymal stromal cells retrovirally transduced with prodrug-converting genes are suitable vehicles for cancer gene therapy.
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Mesenchymal stromal cells retrovirally transduced with prodrug-converting genes are suitable vehicles for cancer gene therapy.

机译：用前药转化基因逆转录病毒转导的间充质基质细胞是用于癌症基因治疗的合适载体。

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摘要

Mesenchymal stem/stromal cells (MSC) possess a set of several fairly unique properties which make them ideally suitable both for cellular therapies and regenerative medicine. These include: relative ease of isolation, the ability to differentiate along mesenchymal and non-mesenchymal lineages in vitro and the ability to be extensively expanded in culture without a loss of differentiative capacity. MSC are not only hypoimmunogenic, but they mediate immunosuppression upon transplantation, and possess pronounced anti-inflammatory properties. They are able to home to damaged tissues, tumors, and metastases following systemic administration. The ability of homing holds big promise for tumor-targeted delivery of therapeutic agents. Viruses are naturally evolved vehicles efficiently transferring their genes into host cells. This ability made them suitable for engineering vector systems for the delivery of genes of interest. MSC can be retrovirally transduced with genes encoding prodrug-converting genes (suicide genes), which are not toxic per se, but catalyze the formation of highly toxic metabolites following the application of a nontoxic prodrug. The homing ability of MSC holds advantages compared to virus vehicles which display many shortcomings in effective delivery of the therapeutic agents. Gene therapies mediated by viruses are limited by their restricted ability to track cancer cells infiltrating into the surrounding tissue, and by their low migratory capacity towards tumor. Thus combination of cellular therapy and gene delivery is an attractive option - it protects the vector from immune surveillance, and supports targeted delivery of a therapeutic gene/protein to the tumor site.
机译：间充质干/基质细胞（MSC）具有一系列相当独特的性质，使其非常适合用于细胞疗法和再生医学。这些包括：相对容易分离，在体外沿间充质和非间充质谱系分化的能力以及在培养中广泛扩增而又不丧失分化能力的能力。 MSC不仅具有低免疫原性，而且在移植时介导免疫抑制，并具有明显的抗炎特性。在全身性给药后，它们能够适应受损的组织，肿瘤和转移灶。归巢的能力对于以肿瘤为目标的治疗剂的传递具有广阔的前景。病毒是自然进化的媒介，可有效地将其基因转移到宿主细胞中。这种能力使它们适合用于传递目标基因的工程载体系统。 MSC可以用编码前药转化基因（自杀基因）的基因进行逆转录病毒转导，该基因本身无毒，但在应用无毒前药后可催化高毒性代谢物的形成。与病毒载体相比，MSC的归巢能力具有优势，而病毒载体在有效递送治疗剂方面显示出许多缺点。病毒介导的基因疗法受到追踪癌细胞浸润到周围组织的能力的限制，以及对肿瘤的低迁移能力。因此，细胞疗法和基因传递的结合是一个有吸引力的选择-它可以保护载体免受免疫监视，并支持将治疗性基因/蛋白质靶向传递至肿瘤部位。

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