Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2005-11-9
pubmed:abstractText
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 (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([(18)F]-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 [(18)F]-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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7749-56
pubmed:dateRevised
2009-5-22
pubmed:meshHeading
pubmed-meshheading:16278396-Animals, pubmed-meshheading:16278396-Antigens, CD31, pubmed-meshheading:16278396-Cell Line, Tumor, pubmed-meshheading:16278396-Cell Membrane, pubmed-meshheading:16278396-Cell Proliferation, pubmed-meshheading:16278396-Cytokines, pubmed-meshheading:16278396-Flow Cytometry, pubmed-meshheading:16278396-Gene Therapy, pubmed-meshheading:16278396-Genes, Reporter, pubmed-meshheading:16278396-Genetic Vectors, pubmed-meshheading:16278396-Green Fluorescent Proteins, pubmed-meshheading:16278396-Humans, pubmed-meshheading:16278396-Immunohistochemistry, pubmed-meshheading:16278396-Lentivirus, pubmed-meshheading:16278396-Mesoderm, pubmed-meshheading:16278396-Mice, pubmed-meshheading:16278396-Neoplasm Transplantation, pubmed-meshheading:16278396-Neoplasms, pubmed-meshheading:16278396-Polymerase Chain Reaction, pubmed-meshheading:16278396-Positron-Emission Tomography, pubmed-meshheading:16278396-Protein Biosynthesis, pubmed-meshheading:16278396-Stem Cells, pubmed-meshheading:16278396-Time Factors
pubmed:year
2005
pubmed:articleTitle
Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging.
pubmed:affiliation
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't