Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
PLoS One. 2012;7(7):e39119. doi: 10.1371/journal.pone.0039119. Epub 2012 Jul 24.
Endostatin is an important endogenous inhibitor of neovascularization that has been widely used in anti-angiogenesis therapy for the treatment of cancer. However, its clinical application is largely hampered by its low efficacy. Human placenta-derived mesenchymal stem cells (hpMSCs) are particularly attractive cells for clinical use in cell-based therapies. In the present study, hpMSCs were isolated and characterized. We then evaluated the tumor targeting properties and antitumor effects of hpMSCs as gene delivery vehicles for ovarian cancer therapy. We efficiently engineered hpMSCs to deliver endostatin via adenoviral transduction mediated by Lipofectamine 2000. The tropism capacity of the engineered hpMSCs toward tumor cells was then confirmed by in vitro migration assays and in vivo by intraperitoneal injection of hpMSCs into nude mice. The hpMSCs expressing the human endostatin gene demonstrated preferential homing to the tumor site and significantly decreased the tumor volume without apparent systemic toxic effects. These observations were associated with significantly decreased blood sprouts and tumor cell proliferation as well as a dramatically increased tumor apoptosis index. These results suggested that hpMSCs are potentially an effective delivery vehicle for therapeutic genes for the treatment of ovarian cancer.
内皮抑素是一种重要的内源性血管生成抑制剂，已广泛应用于癌症的抗血管生成治疗。然而，其临床应用在很大程度上受到其疗效低的限制。人胎盘间充质干细胞（hpMSCs）是细胞治疗中临床应用特别有吸引力的细胞。在本研究中，分离和鉴定了 hpMSCs。然后，我们评估了 hpMSCs 作为卵巢癌治疗的基因递送载体的肿瘤靶向特性和抗肿瘤作用。我们通过 Lipofectamine 2000 介导的腺病毒转导有效地对 hpMSCs 进行了内皮抑素的传递。通过体外迁移实验和 hpMSCs 腹腔内注射到裸鼠体内，然后确认了工程化 hpMSCs 对肿瘤细胞的趋向能力。表达人内皮抑素基因的 hpMSCs 表现出对肿瘤部位的优先归巢，并显著降低肿瘤体积，而没有明显的全身毒性作用。这些观察结果与明显减少的血管芽和肿瘤细胞增殖以及显著增加的肿瘤细胞凋亡指数相关。这些结果表明，hpMSCs 可能是治疗卵巢癌的治疗基因的有效递送载体。
