The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Mesenchymal Stem Cell Targeting of Microscopic Tumors and Tumor Stroma Development Monitored by Noninvasive In vivo Positron Emission Tomography Imaging
Open accessAbstract
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 <2 weeks in tumor fragments transplanted into secondary hosts. We conclude that hMSCs can target microscopic tumors, subsequently proliferate and differentiate, and contribute to formation of a significant portion of tumor stroma. PET imaging should facilitate clinical translation of stem cell–based anticancer gene therapeutic approaches by providing the means for in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing “tracer” hMSCs in tumor stroma.
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“MSC can be mobilized and recruited to active tumor sites, where they can incorporate into the tumor’s microenvironment [5, 68, 100–103].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [103]
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Metadata
- Authors
- Hung, S.-C., Deng, W.-P., Yang, W. K., Liu, R.-S., Lee, C.-C., Su, T.-C., Lin, R.-J., Yang, D.-M., Chang, C.-W., Chen, W.-H., Wei, H.-J., & Gelovani, J. G.
- Affiliations
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Taipei Medical University (TW)
- Taipei Veterans General Hospital (TW)
- 2Institute of Biomedical Materials, Taipei Medical University; Departments of
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Clinical Cancer Research
- Published
- 2005-11-01
- Volume
- 11
- Issue
- 21
- Pages
- 7749-7756
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2149287721
- Cited by
- 268
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 19 · 2015: 17 · 2014: 15 · 2013: 29 · 2012: 19
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, Los Angeles
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- mesenchymal stem cells, tumor targeting, tumor stroma, HSV-1 thymidine kinase, suicide gene therapy, cytokine gene therapy, 18F-FHBG, stem cell differentiation, endothelial cells, colon cancer, HT-29 cells, non-invasive imaging, stem cell trafficking
- MeSH terms
- Animals, Cell Membrane, Flow Cytometry, Genetic Vectors, Humans, Immunohistochemistry, Mesoderm, Neoplasm Transplantation, Neoplasms, Stem Cells, Time Factors, Protein Biosynthesis, Genetic Therapy, Lentivirus, Polymerase Chain Reaction, Cytokines, Genes, Reporter, Platelet Endothelial Cell Adhesion Molecule-1, Cell Line, Tumor, Cell Proliferation, Positron-Emission Tomography, Green Fluorescent Proteins, Mice
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