Cardiovascular Research Center (CSIC-ICCC), CIBER-BBN, Barcelona, Spain.
Gene Ther. 2009 Apr;16(4):547-57. doi: 10.1038/gt.2008.176. Epub 2008 Dec 18.
Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for localized tumor therapy. We demonstrate a model for tumor therapy development based on the use of AMSCs expressing renilla luciferase and thymidine kinase, as cellular vehicles for ganciclovir-mediated bystander killing of firefly luciferase expressing tumors, and noninvasive bioluminescence imaging to continuously monitor both, tumor cells and AMSCs. We show that the therapy delivering AMSCs survive long time within tumors, optimize the ratio of AMSCs to tumor cells for therapy, and asses the therapeutic effect in real time. Treatment of mice bearing prostate tumors plus therapeutic AMSCs with the prodrug ganciclovir induced bystander killing effect, reducing the number of tumor cells to 1.5 % that of control tumors. Thus, AMSCs could be useful vehicles to deliver localized therapy, with potential for clinical application in inoperable tumors and surgical borders after tumor resection. This approach, useful to evaluate efficiency of therapeutic models, should facilitate the selection of cell types, dosages, therapeutic agents and treatment protocols for cell-based therapies of specific tumors.
人脂肪组织间充质基质细胞（AMSCs）与骨髓间充质基质细胞具有共同的特征，包括相似的分化潜能和细胞表面标志物。由于其普遍存在、更高的丰度和易于分离，AMSCs 可能是局部肿瘤治疗的方便的自体递送载体。我们展示了一种基于表达海肾荧光素酶和胸苷激酶的 AMSCs 的肿瘤治疗开发模型，作为萤火虫荧光素酶表达肿瘤的更昔洛韦介导的旁观者杀伤的细胞载体，并通过非侵入性生物发光成像连续监测肿瘤细胞和 AMSCs。我们表明，治疗性 AMSCs 在肿瘤内长时间存活，优化了用于治疗的 AMSCs 与肿瘤细胞的比例，并实时评估治疗效果。用前药更昔洛韦治疗携带前列腺肿瘤的小鼠和治疗性 AMSCs 诱导旁观者杀伤效应，将肿瘤细胞数量减少到对照组肿瘤的 1.5%。因此，AMSCs 可以作为局部治疗的有用载体，具有在不可手术肿瘤和肿瘤切除后的手术边界处进行临床应用的潜力。这种方法有助于评估治疗模型的效率，应该有利于选择特定肿瘤的细胞类型、剂量、治疗剂和细胞治疗方案。
