Cited by 268Mesenchymal stem cell researchCancer Research and TreatmentsAngiogenesis and VEGF in Cancer

Mesenchymal Stem Cell Targeting of Microscopic Tumors and Tumor Stroma Development Monitored by Noninvasive In vivo Positron Emission Tomography Imaging

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Hung, Shih-Chieh, Deng, Win-Ping, Yang, Wen K., Liu, Ren-Shyan, Lee, Chien-Chih, Su, Tzu-Chi, Lin, Rue-Jen, Yang, Den-Mei +4 more·2005·Clinical Cancer Research

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 <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 become part of the tumor microenvironment.

    “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]

    The Discussion (p. 7) reports that intravenously administered human MSCs engrafted in microscopic tumors and contributed to tumor stroma, supporting recruitment and incorporation. It also says that whether tumors mobilize endogenous MSCs from bone marrow remains undetermined, so the mobilization part is not established by this study. (LLM, conf=0.88)

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Research works printed but not linked: 7

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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
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of California, Los Angeles
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
  • 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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