Mesenchymal Stem Cell Targeting of Microscopic Tumors and Tumor Stroma Development Monitored by Noninvasive In vivo Positron Emission Tomography Imaging
Open Access
- 1 November 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 11 (21), 7749-7756
- https://doi.org/10.1158/1078-0432.ccr-05-0876
Abstract
The aim of this study was to assess the efficacy human mesenchymal stem cells (hMSC) for targeting microscopic tumors and suicide gene or cytokine gene therapy. Immunodeficient mice were transplanted s.c. with human colon cancer cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with “tracer” hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced green fluorescent protein (EGFP) reporter genes. Subsequently, these tumors were examined for specificity and magnitude of HSV1-TK+, EGFP+ stem cell engraftment and proliferation in tumor stroma by in vivo positron emission tomography (PET) with 18F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([18F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the presence of HSV1-TK+ tumor stroma with an average of 0.36 ± 0.24% ID/g [18F]-FHBG accumulation. In vivo imaging results were validated by in situ correlative histochemical, immunofluorescent, and cytometric analyses, which revealed EGFP expression in vWF+ and CD31+ endothelial cells of capillaries and larger blood vessels, in germinal layer of dermis and hair follicles proximal to the s.c. tumor site. These differentiated HSV1-TK+, GFP+ endothelial cells had limited proliferative capacity and a short life span of in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing “tracer” hMSCs in tumor stroma.Keywords
This publication has 37 references indexed in Scilit:
- Molecular Imaging of Temporal Dynamics and Spatial Heterogeneity of Hypoxia-Inducible Factor-1 Signal Transduction Activity in Tumors in Living MiceCancer Research, 2004
- Differential Transplantability of Tumor-Associated Stromal CellsCancer Research, 2004
- Quantitation of cell number by a positron emission tomography reporter gene strategyMolecular Imaging & Biology, 2004
- Immortalization without neoplastic transformation of human mesenchymal stem cells by transduction with HPV16 E6/E7 genesInternational Journal of Cancer, 2004
- Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stromaProceedings of the National Academy of Sciences of the United States of America, 2003
- Stem Cell MobilizationHematology-American Society Hematology Education Program, 2003
- In Vitro Differentiation of Size‐Sieved Stem Cells into Electrically Active Neural CellsThe International Journal of Cell Cloning, 2002
- RNA 3′ Readthrough of Oncoretrovirus and Lentivirus: Implications for Vector Safety and EfficacyJournal of Virology, 2002
- Suicide gene transduction sensitizes murine embryonic and human mesenchymal stem cells to ablation on demand – a fail-safe protection against cellular misbehaviorGene Therapy, 2002
- Tumor Angiogenesis: Therapeutic ImplicationsNew England Journal of Medicine, 1971