Open AccessTrafficking Mesenchymal Stem Cell Engraftment and Differentiation in Tumor‐Bearing Mice by Bioluminescence Imaging
Author(s) -
Wang Hui,
Cao Feng,
De Abhijit,
Cao Yuan,
Contag Christopher,
Gambhir Sanjiv S.,
Wu Joseph C.,
Chen Xiaoyuan
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.81
Subject(s) - bioluminescence imaging , mesenchymal stem cell , green fluorescent protein , biology , cancer research , reporter gene , microbiology and biotechnology , luciferase , pathology , cell culture , transfection , gene expression , medicine , gene , biochemistry , genetics
The objective of the study was to track the distribution and differentiation of mesenchymal stem cells (MSCs) in tumor‐bearing mice. The 4T1 murine breast cancer cells were labeled with renilla luciferase‐monomeric red fluorescence protein (rLuc‐mRFP) reporter gene. The MSCs labeled with firefly luciferase‐enhanced green fluorescence protein (fLuc‐eGFP) reporter gene (MSCs‐R) were isolated from L2G85 transgenic mice that constitutively express fLuc‐eGFP reporter gene. To study the tumor tropism of MSCs, we established both subcutaneous and lung metastasis models. In lung metastasis tumor mice, we injected MSCs‐R intravenously either on the same day or 4 days after 4T1 tumor cell injection. In subcutaneous tumor mice, we injected MSCs‐R intravenously 7 days after subcutaneous 4T1 tumor inoculation. The tumor growth was monitored by rLuc bioluminescence imaging (BLI). The fate of MSCs‐R was monitored by fLuc BLI. The localization of MSCs‐R in tumors was examined histologically. The osteogenic and adipogenic differentiation of MSCs‐R was investigated by alizarin red S and oil red O staining, respectively. The mechanism of the dissimilar differentiation potential of MSCs‐R under different tumor microenvironments was investigated. We found that the 4T1 cells were successfully labeled with rLuc‐mRFP. The MSCs‐R isolated from L2G85 transgenic mice constitutively express fLuc‐eGFP reporter gene. When injected intravenously, MSCs‐R survived, proliferated, and differentiated in tumor sites but not elsewhere. The localization of GFP + MSCs‐R in tumor lesions was confirmed ex vivo. In conclusion, the MSCs‐R can selectively localize, survive, and proliferate in both subcutaneous tumor and lung metastasis as evidenced by noninvasive bioluminescence imaging and ex vivo validation. The MSCs‐R migrated to lung tumor differentiated into osteoblasts, whereas the MSCs‐R targeting subcutaneous tumor differentiated into adipocytes. STEM CELLS 2009;27:1548–1558