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Published on: March 1, 2020
Antitumor activities of human placenta-derived mesenchymal stem cells expressing endostatin on ovarian cancer
Lan Zheng1, Dongmei Zhang, Xiancheng Chen
1Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Abstract:
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.
Insights
Engineered human placenta-derived mesenchymal stem cells (hpMSCs) effectively deliver endostatin to ovarian tumors, reducing tumor volume and growth. This approach shows promise for targeted cancer gene therapy.
Area of Science:
- Oncology
- Regenerative Medicine
- Gene Therapy
Background:
- Endostatin is an endogenous inhibitor of neovascularization used in anti-angiogenesis cancer therapy.
- Clinical use of endostatin is limited by low efficacy.
- Human placenta-derived mesenchymal stem cells (hpMSCs) are suitable for cell-based therapies.
Purpose of the Study:
- To evaluate hpMSCs as gene delivery vehicles for ovarian cancer.
- To assess the tumor-targeting and anti-tumor effects of engineered hpMSCs delivering endostatin.
Main Methods:
- hpMSCs were isolated, characterized, and engineered to express endostatin using adenoviral transduction.
- In vitro migration assays and in vivo studies in nude mice were performed.
- Tumor volume, blood vessel formation, cell proliferation, and apoptosis were analyzed.
Main Results:
- Engineered hpMSCs demonstrated tropism towards tumor cells in vitro and in vivo.
- Intraperitoneal administration of engineered hpMSCs significantly reduced ovarian tumor volume.
- Reduced tumor vascularization and proliferation, with increased apoptosis, were observed without systemic toxicity.
Conclusions:
- hpMSCs engineered to deliver endostatin exhibit tumor-homing capabilities.
- This strategy offers a potential effective gene delivery system for ovarian cancer treatment.
- hpMSCs represent a promising platform for targeted anti-angiogenesis gene therapy.
