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Exploring the Potential of Mesenchymal Stem Cell Sheet on The Development of Hepatocellular Carcinoma In Vivo
Published on: September 11, 2018
Human mesenchymal stem cells overexpressing pigment epithelium-derived factor inhibit hepatocellular carcinoma in
1Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
Abstract:
The poor outcome of cancer gene therapy in clinical trials relates in part to insufficient gene delivery to tumor sites. Mesenchymal stem cells (MSCs) represent a new tool for the delivery of therapeutic agents to tumor cells. This study used an orthotopic nude mice model of hepatocellular carcinoma (HCC) to evaluate the potential of genetically modified human MSCs (hMSCs), to function as an effective delivery vehicle for therapeutic genes. hMSCs derived from the bone marrow were efficiently engineered to express human pigment epithelium-derived factor (PEDF) by lentiviral transduction, then tested in vitro for high-level expression and bioactivity of the transgenic protein. The preferential homing of hMSCs toward HCC was confirmed by in vitro and in vivo migration assays. in vivo efficacy experiments showed that intravenous (i.v.) injection of PEDF-expressing hMSCs significantly suppressed both the growth of primary liver tumors and the development of pulmonary metastases. Moreover, hMSCs-based PEDF gene delivery moderately increased the systemic levels of human PEDF. Immunohistochemistry of primary liver tumors demonstrated lower microvessel density in mice treated with hMSCs-PEDF than in control mice. This is the first study to show the potential of hMSCs as an effective delivery vehicle for therapeutic genes in the treatment of HCC.
Insights
Genetically modified mesenchymal stem cells (MSCs) effectively delivered therapeutic genes to liver cancer (HCC) in mice. This approach suppressed tumor growth and metastasis, showing promise for cancer gene therapy.
Area of Science:
- Oncology
- Stem Cell Biology
- Gene Therapy
Background:
- Cancer gene therapy faces challenges with effective gene delivery to tumors.
- Mesenchymal stem cells (MSCs) show potential as targeted delivery vehicles for therapeutic agents.
Purpose of the Study:
- To evaluate genetically modified human MSCs (hMSCs) as a delivery system for therapeutic genes in hepatocellular carcinoma (HCC).
- To assess the efficacy of hMSCs engineered to express pigment epithelium-derived factor (PEDF) in an HCC mouse model.
Main Methods:
- Human MSCs (hMSCs) were engineered using lentiviral transduction to express human PEDF.
- In vitro and in vivo assays confirmed hMSC homing to HCC.
- The anti-tumor effects of intravenous injection of PEDF-expressing hMSCs were evaluated in an orthotopic HCC nude mouse model.
Main Results:
- Engineered hMSCs demonstrated high-level PEDF expression and bioactivity.
- hMSCs showed preferential homing to HCC tumors.
- Treatment with PEDF-expressing hMSCs significantly suppressed primary tumor growth and pulmonary metastases.
- Reduced tumor microvessel density was observed in treated mice.
Conclusions:
- Genetically modified hMSCs can serve as an effective delivery vehicle for therapeutic genes in HCC treatment.
- hMSC-mediated PEDF delivery shows significant therapeutic potential against liver cancer and metastasis.
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