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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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Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052
Tumor angiogenesis: therapeutic implications
Sherwood, L. M., Parris, E. E., & Folkman, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197111182852108 · Cited by 10,187
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
Bone marrow cells regenerate infarcted myocardium
Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J. M., McKay, R. D. G., Nadal‐Ginard, B., Bodine, D. M., et al. (2001) · Nature · doi:10.1038/35070587 · Cited by 5,149
Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues
Prockop, D. J. (1997) · Science · doi:10.1126/science.276.5309.71 · Cited by 4,629
Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF
Holash, J. A., Maisonpierre, P. C., Compton, D. L., Boland, P., Alexander, C., Zagzag, D., Yancopoulos, G. D., & Wiegand, S. J. (1999) · Science · doi:10.1126/science.284.5422.1994 · Cited by 2,222
Genes Expressed in Human Tumor Endothelium
Croix, B. S., Rago, C., Velculescu, V. E., Traverso, G., Romans, K. E., Montgomery, E. A., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., et al. (2000) · Science · doi:10.1126/science.289.5482.1197 · Cited by 1,859
Aboody, K. S., Brown, A. B., Rainov, N. G., Bower, K. A., Liu, S., Yang, W., Small, J. E., Herrlinger, U., Ourednik, V., Black, P. M., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12846 · Cited by 1,207
Self-citationOrigin of endothelial progenitors in human postnatal bone marrow
Reyes, M., Dudek, A. Z., Jahagirdar, B., Koodie, L., Marker, P. H., & Verfaillie, C. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14327 · Cited by 1,105
(2002) · PubMed · Cited by 903
Origin of endothelial progenitors in human postnatal bone marrow
Reyes, M., Dudek, A. Z., Jahagirdar, B., Koodie, L., Marker, P. H., & Verfaillie, C. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214327 · Cited by 887
Relf, M., LeJeune, S., Scott, P. A. E., Fox, S. B., Smith, K. A., Leek, R., Moghaddam, A., Whitehouse, R. M., Bicknell, R., & Harris, A. L. (1997) · PubMed · Cited by 833
Mesenchymal stem cells in bone development, bone repair, and skeletal regenaration therapy
Bruder, S. P., Fink, D. J., & Caplan, A. I. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240560303 · Cited by 712
Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model
Nakamura, K., Ito, Y., Kawano, Y., Kurozumi, K., Kobune, M., Tsuda, H., Bizen, A., Honmou, O., Niitsu, Y., & Hamada, H. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302276 · Cited by 597
Palma, M. D., Venneri, M. A., Roca, C., & Naldini, L. (2003) · Nature Medicine · doi:10.1038/nm871 · Cited by 546
Spees, J. L., Olson, S. D., Ylöstalo, J., Lynch, P. J., Smith, J. R., Perry, A. S., Peister, A., Wang, M. Y., & Prockop, D. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437997100 · Cited by 508
Gambhir, S. S., Bauer, E. M., Black, M. E., Liang, Q., Kokoris, M. S., Barrio, J. R., Iyer, M. R., Namavari, M., Phelps, M. E., & Herschman, H. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2785 · Cited by 450
Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography.
Tjuvajev, J. G., Avril, N. E., Oku, T., Sasajima, T., Miyagawa, T., Joshi, R., Safer, M. L., Beattie, B. J., DiResta, G. R., Daghighian, F., et al. (1998) · PubMed · Cited by 375
Imaging tri-fusion multimodality reporter gene expression in living subjects
Ray, P., De, A., Min, J.-J., Tsien, R. Y., & Gambhir, S. S. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1816 · Cited by 329
Wu, J. C., Chen, I. Y., Sundaresan, G., Min, J., De, A., Qiao, J.-H., Fishbein, M. C., & Gambhir, S. S. (2003) · Circulation · doi:10.1161/01.cir.0000091252.20010.6e · Cited by 285
Isolation and Characterization of Size‐Sieved Stem Cells from Human Bone Marrow
Hung, S., Chen, N., Hsieh, S.-L. E., Li, H., Ma, H., & Lo, W. (2002) · Stem Cells · doi:10.1634/stemcells.20-3-249 · Cited by 276
Self-citationGelovani, J. G., Doubrovin, M., Akhurst, T., Cai, S., Balatoni, J., Alauddin, M. M., Finn, R. D., Bornmann, W. G., Thaler, H. T., Conti, P. S., et al. (2002) · PubMed · Cited by 270
Self-citationCottler‐Fox, M., Lapidot, T., Petit, I., Kollet, Ó., DiPersio, J. F., Link, D. C., & Devine, S. M. (2003) · Hematology · doi:10.1182/asheducation-2003.1.419 · Cited by 241
Koehne, G., Doubrovin, M., Doubrovina, E. S., ZANZONICO, P. B., Gallardo, H. F., Ivanova, A. E., Balatoni, J., Teruya‐Feldstein, J., Heller, G., May, C., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt805 · Cited by 221
Self-citationImaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo
Doubrovin, M., Ponomarev, V., Beresten, T., Balatoni, J., Bornmann, W. G., Finn, R. D., Humm, J. L., Larson, S. M., Sadelain, M., Blasberg, R. G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161091198 · Cited by 210
Self-citationRay, P., Wu, A. M., & Gambhir, S. S. (2003) · PubMed · Cited by 182
Serganova, I. S., Doubrovin, M., Vider, J., Ponomarev, V., Soghomonyan, S., Beresten, T., Ageyeva, L., Serganov, A., Cai, S., Balatoni, J., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0842 · Cited by 178
Self-citationJin, H. K., Carter, J. E., Huntley, G. W., & Schuchman, E. H. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14862 · Cited by 178
In Vitro Differentiation of Size‐Sieved Stem Cells into Electrically Active Neural Cells
Hung, S., Cheng, H., Pan, C., Tsai, M. J., Kao, L., & Ma, H. (2002) · Stem Cells · doi:10.1634/stemcells.20-6-522 · Cited by 153
Self-citationQuantitative imaging of the T cell antitumor response by positron-emission tomography
Dubey, P., Su, H. C., Adonai, N., Du, S., Rosato, A., Braun, J. G., Gambhir, S. S., & Witte, O. N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337418100 · Cited by 143
RNA 3′ Readthrough of Oncoretrovirus and Lentivirus: Implications for Vector Safety and Efficacy
Zaiss, A. K., Son, S., & Chang, L. (2002) · Journal of Virology · doi:10.1128/jvi.76.14.7209-7219.2002 · Cited by 135
Jacobs, A., Dubrovin, M., Hewett, J., Sena‐Esteves, M., Tan, C., Slack, M., Sadelain, M., Breakefield, X. O., & Gelovani, J. G. (1999) · Neoplasia · doi:10.1038/sj.neo.7900007 · Cited by 116
Self-citationHung, S., Yang, D.-M., Chang, C., Lin, R., Wang, J., Ho, L. L.-T., & Yang, W. K. (2004) · International Journal of Cancer · doi:10.1002/ijc.20126 · Cited by 94
Self-citationJockusch, H., Voigt, S., & Eberhard, D. (2003) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540305100315 · Cited by 67
Quantitation of cell number by a positron emission tomography reporter gene strategy
Su, H. (2004) · Molecular Imaging and Biology · doi:10.1016/j.mibio.2004.02.001 · Cited by 63
Wen, B., Burgman, P., ZANZONICO, P. B., O’Donoghue, J. A., Cai, S., Finn, R., Serganova, I. S., Blasberg, R. G., Gelovani, J. G., Li, G. C., et al. (2004) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-004-1673-z · Cited by 55
Self-citationMersmann, M., Schmidt, A., Rippmann, J. F., W�est, T., Brocks, B., Rettig, W. J., Garin‐Chesa, P., Pfizenmaier, K., & Moosmayer, D. (2001) · International Journal of Cancer · doi:10.1002/1097-0215(200102)9999:9999 · Cited by 52
Self-citationDifferential Transplantability of Tumor-Associated Stromal Cells
Duda, D. G., Fukumura, D., Munn, L. L., Booth, M. F., Brown, E. B., Huang, P., Seed, B., & Jain, R. K. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1268 · Cited by 49
Pragmatic fully 3D image reconstruction for the MiCES mouse imaging PET scanner
Lee, K., Kinahan, P. E., Fessler, J. A., Miyaoka, R. S., Janes, M. L., & Lewellen, T. K. (2004) · Physics in Medicine and Biology · doi:10.1088/0031-9155/49/19/008 · Cited by 44
Fareed, M., & Moolten, F. L. (2002) · Gene Therapy · doi:10.1038/sj.gt.3301771 · Cited by 44
Alauddin, M. M., Shahinian, A. H., Park, R., Tohme, M. S., Fissekis, J. D., & Conti, P. S. (2004) · PubMed · Cited by 43
Deng, W., Yang, W., Lai, W., Liu, R.-S., Hwang, J., Yang, D.-M., Fu, Y.-K., & Wang, H.-E. (2003) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-003-1269-z · Cited by 39
Self-citationMiyagawa, M., Anton, M., Haubner, R., Simões, M. V., Städele, C., Erhardt, W. D., Reder, S., Lehner, T., Wagner, B., Noll, S., et al. (2004) · PubMed · Cited by 33
Lentiviral Vectors: Preparation and Use
Chang, L., & Zaiss, A. K. (2003) · Humana Press eBooks · doi:10.1385/1-59259-141-8:303 · Cited by 32
Shiue, G. G., Shiue, C., Lee, R. L., MacDonald, D., Hustinx, R., Eck, S. L., & Alavi, A. A. (2001) · Nuclear Medicine and Biology · doi:10.1016/s0969-8051(01)00253-0 · Cited by 31
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Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., Richardson, A. L., Polyak, K., Tubo, R., & Weinberg, R. A. (2007) · Nature · doi:10.1038/nature06188 · Cited by 3,206
Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells
Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., Ganesan, S., Glod, J. W., & Banerjee, D. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0943 · Cited by 912
Fass, L. (2008) · Molecular Oncology · doi:10.1016/j.molonc.2008.04.001 · Cited by 855
Spaeth, E. L., Dembinski, J. L., Sasser, A. K., Watson, K., Klopp, A., Hall, B., Andreeff, M., & Marini, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004992 · Cited by 807
“These data were confirmed in other tumor models [31,32], most recently by Weinberg et al.”
ResultKidd, S. M., Spaeth, E. L., Dembinski, J. L., Dietrich, M. F., Watson, K., Klopp, A. H., Battula, V. L., Weil, M., Andreeff, M., & Marini, F. C. (2009) · Stem Cells · doi:10.1002/stem.187 · Cited by 680
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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