Intratracheal delivery of CX3CL1-expressing mesenchymal stem cells to multiple lung tumors.
The lung is one of the organs to which cancers from solid tumors frequently metastasize. Multiple tumors in the lung are usually treated by systemic chemotherapy because of the lack of efficient methods of targeting antitumor agents to the lung. Although intratracheal administration is an ideal route for targeting multiple lung tumors, antitumor agents are often harmful to the organ or induce inflammation. Mesenchymal stem cells (MSCs), nonhematopoietic stem cells capable of differentiating into various mesoderm-type cells, have a propensity to migrate to and proliferate in tumor tissues after systemic administration. We intratracheally injected MSCs expressing CX3CL1 (MSC/RGDFKN) into the lung of lung tumor-bearing mice with multiple metastases of C26 or Lewis lung carcinoma (LLC). Antitumor effects were evaluated by counting the number of lung metastases and survival. We demonstrated the tropism of mouse MSCs to lung tumor tissues after intratracheal administration of GFP-positive MSCs. Intratracheal injection of MSC/RGDFKN strongly inhibited growth of lung metastases of C26 or LLC, and thus prolonged survival. Intratracheal injection of MSC/RGDFKN did not induce an inflammatory reaction in the lung. These results suggest that MSCs expressing antitumor agents can be delivered intratracheally into multiple lung tumor tissues without causing inflammation.
Xin
Hong
H
Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Sun
Ruowen
R
Kanehira
Masahiko
M
Takahata
Takenori
T
Itoh
Jugoh
J
Mizuguchi
Hiroyuki
H
Saijo
Yasuo
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D041702:BALB 3T3 Cells; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000556:secondary* / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D054428:Chemokine CX3CL1 / Q000096:biosynthesis* / Q000235:genetics; D003627:Data Interpretation, Statistical; D004333:Drug Administration Routes; D006651:Histocytochemistry; D053208:Kaplan-Meier Estimate; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014132:Trachea
D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse