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Open Access Publications from the University of California

Mesenchymal stem cells as vehicles for targeted delivery of antiangiogenic protein to solid tumors.

  • Author(s): Wu, Jian
  • Ghaedi, Mahboobe
  • et al.

Published Web Location

BACKGROUND/AIMS: 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 be 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 in comparison to untransduced hMSCs. Our data demonstrate for the first time that genetically-modified hMSCs released abundant and functional AAT that caused obvious cytotoxicity to HUVEC. CONCLUSION: hMSC may serve as an effective platform for the targeted delivery of therapeutic proteins to cancer sites. Copyright © 2011 John Wiley & Sons, Ltd.

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