Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells.
MSCs are nonhematopoietic 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 i.v. injection of green fluorescent protein-positive MSCs in vivo. We transduced CX3CL1 (fractalkine), an immunostimulatory chemokine, to the mouse MSCs ex vivo using an adenoviral vector with the Arg-Gly-Asp-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. Disclosure of potential conflicts of interest is found at the end of this article.
Xin
Hong
H
Department of Molecular Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi Aobaku, Sendai 980-8575, Japan.
Kanehira
Masahiko
M
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Kikuchi
Toshiaki
T
Nukiwa
Toshihiro
T
Saijo
Yasuo
Y
D016475:3T3 Cells; D000256:Adenoviridae; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000378:metabolism; D009928:Organ Specificity; D014161:Transduction, Genetic; D018523:Tropism; D001616:beta-Galactosidase / Q000378:metabolism
D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D001616:beta-Galactosidase