Targeted-Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells

¹ Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
² Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
³ Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan
⁴ Pharmaceutical and Medical Agency, Tokyo, Japan
⁵ Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan

^* To whom correspondence should be addressed. E-mail: yasosj{at}idac.tohoku.ac.jp.

	Abstract

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells capable of differentiating into various mesoderm-type cells. MSCs have been considered to be a potential vehicle for cell based gene therapy because MSCs are relatively easily expanded in vitro and have the propensity to migrate to and proliferate in the tumor tissue after systemic administration. Here, we demonstrated the tropism of mouse MSCs to tumor cells in vitro and multiple tumor tissues in the lung after intravenous injection of GFP positive MSCs in vivo. We transduced CX3CL1 (fractalkine), an immunostimulatory chemokine, to the mouse MSCs ex vivo using an adenoviral vector with the RGD-4C peptide in the fiber knob. Intravenous injection of CX3CL1-expressing MSCs to the mice bearing lung metastases of C26 and B16F10 cells strongly inhibited the development of lung metastases and thus prolonged the survival of these tumor bearing mice. This antitumor effect depended on both innate and adaptive immunity. These results suggest that MSCs can be used as a vehicle for introducing biological agents into multiple lung tumor tissues.

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