Related Experiment Video
Updated: Jun 3, 2026
Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
Published on: September 27, 2013
Mesenchymal stem cells as vehicles for targeted delivery of anti-angiogenic protein to solid tumors
Mahboobe Ghaedi1, Masoud Soleimani, Narges Mohammad Taghvaie
1Department of Internal Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
Background:
Inhibition of tumor-induced angiogenesis may restrict tumor growth and metastasis. Long-term systemic delivery of angiogenic inhibitors is associated with toxicity, as well as other severe side-effects. The utility of cells as vehicles for gene therapy to deliver therapeutic molecules has been suggested to represent an efficient approach. Mesenchymal stem cells (MSCs) exhibit a tropism to cancer tissue, and may serve as a cellular delivery vehicle and a local producer of anti-angiogenic agents.
Methods:
In the present study, we attempted to assess production of the transgene, α1-antitrypsin (AAT), in lentivirus-transduced human MSCs and its cytotoxicity against human umbilical cord vein endothelial cells (HUVEC). The secreted protein from these effector cells was determined by an enzyme-linked immunosorbent assay. The cytotoxicity of hMSCs that overexpress the human AAT gene against HUVEC was evaluated with an apoptotic assay.
Results:
Lentivirus-transduced hMSCs produced functional AAT and displayed much higher cytotoxicity against HUVEC than untransduced hMSCs. Moreover, AAT secreted from transduced hMSCs significantly inhibited HUVEC proliferation compared to untransduced hMSCs. The data obtained demonstrate for the first time that genetically modified hMSCs released abundant and functional AAT that caused obvious cytotoxicity to HUVEC.
Conclusions:
hMSC may serve as an effective platform for the targeted delivery of therapeutic proteins to cancer sites.
Insights
Genetically modified mesenchymal stem cells (MSCs) effectively produce and deliver alpha-1-antitrypsin (AAT) to inhibit blood vessel growth in tumors. This targeted gene therapy approach shows promise for cancer treatment by reducing angiogenesis.
Area of Science:
- Oncology
- Gene Therapy
- Cell Biology
Background:
- Tumor-induced angiogenesis fuels cancer growth and metastasis.
- Systemic delivery of anti-angiogenic drugs causes toxicity.
- Cell-based gene therapy offers a targeted delivery approach.
Purpose of the Study:
- To assess alpha-1-antitrypsin (AAT) production in lentivirus-transduced human mesenchymal stem cells (MSCs).
- To evaluate the cytotoxicity of genetically modified MSCs against human umbilical cord vein endothelial cells (HUVEC).
Main Methods:
- Human MSCs were transduced with lentivirus to express AAT.
- Secreted AAT levels were quantified using ELISA.
- Cytotoxicity against HUVEC was assessed via apoptotic assays.
Main Results:
- Transduced MSCs produced functional AAT.
- Genetically modified MSCs exhibited significantly higher cytotoxicity towards HUVEC.
- Secreted AAT inhibited HUVEC proliferation.
Conclusions:
- Genetically modified MSCs effectively produce and secrete functional AAT.
- MSCs serve as a viable platform for targeted delivery of therapeutic proteins to tumor sites.
- This approach demonstrates potential for anti-angiogenic cancer therapy.
More Related Videos
Related Concept Videos
01:19Mesenchymal Stem Cells
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...