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Therapeutic potential of bone marrow-derived mesenchymal stem cells producing pigment epithelium-derived
Qiaoling Chen1, Ping Cheng, Tao Yin
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, P.R. China.
Abstract:
Specific and efficient gene delivery to target cells and the subsequent expression of the RNA and protein is crucial to the success of gene-based therapy for cancer. Mesenchymal stem cells (MSCs) represent novel and efficient tools for delivery of therapeutic agents to tumor cells. In this study, we evaluated the potential of bone marrow-derived mesenchymal stem cells, genetically modified to express pigment epithelium-derived factor (PEDF) for the treatment of Lewis lung carcinoma (LLC). MSCs derived from murine bone marrow were efficiently engineered to express human PEDF by adenoviral transduction, and the expression and bioactivity of the transgenic protein from engineered MSCs were confirmed in vitro. Animal experiments showed that the systemic administration of MSCs treated with PEDF dramatically reduced the growth of LLC tumors and significantly prolonged survival. Immunohistochemistry analysis of the tumors from MSC-PEDF-treated animals indicated an increase in apoptosis and a decrease in microvessel density. ELISA showed that the group of MSCs treated with PEDF had relatively higher expression levels of PEDF in tumor tissue and lower levels in serum compared with the free Ad-PEDF group. These results suggest that MSCs have potential use as effective delivery of vehicles for therapeutic genes in the treatment of LLC.
Insights
Genetically engineered mesenchymal stem cells (MSCs) expressing pigment epithelium-derived factor (PEDF) effectively treated Lewis lung carcinoma (LLC) in mice. This approach reduced tumor growth and improved survival by enhancing apoptosis and decreasing blood vessel formation.
Area of Science:
- Oncology
- Gene Therapy
- Stem Cell Biology
Background:
- Gene delivery for cancer therapy requires efficient targeting and expression.
- Mesenchymal stem cells (MSCs) show promise as delivery vehicles for cancer therapeutics.
- Pigment epithelium-derived factor (PEDF) has potential anti-tumor properties.
Purpose of the Study:
- To evaluate bone marrow-derived MSCs engineered to express PEDF for Lewis lung carcinoma (LLC) treatment.
- To assess the in vitro expression and bioactivity of PEDF from engineered MSCs.
- To determine the in vivo efficacy of MSC-mediated PEDF delivery in LLC-bearing mice.
Main Methods:
- Murine bone marrow MSCs were genetically modified using adenoviral transduction to express human PEDF.
- In vitro assays confirmed PEDF expression and bioactivity in engineered MSCs.
- Animal studies involved systemic administration of MSC-PEDF for LLC treatment, followed by tumor analysis (immunohistochemistry, ELISA).
Main Results:
- Engineered MSCs efficiently expressed functional PEDF in vitro.
- Systemic administration of MSC-PEDF significantly inhibited LLC tumor growth and prolonged survival in mice.
- Tumor analysis revealed increased apoptosis and reduced microvessel density in MSC-PEDF treated groups.
- Higher PEDF levels were detected in tumor tissue and lower levels in serum for the MSC-PEDF group compared to free Ad-PEDF.
Conclusions:
- MSCs engineered to express PEDF are effective delivery vehicles for cancer gene therapy.
- MSC-PEDF therapy demonstrates anti-tumor effects in LLC by promoting apoptosis and inhibiting angiogenesis.
- This strategy holds potential for developing novel treatments for Lewis lung carcinoma.
