Teratoma
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Studies from M.G. Pomper and colleagues yield new information about gene therapy
2009 JUL 6 - (NewsRx.com) -- "Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase (fLuc) for bioluminescence imaging or the HSV1 thymidine kinase (HSV1-TK) for radiopharmaceutical-based imaging were constructed to monitor human embryonic stem cell (hESC) engraftment and proliferation in live mice after transplantation. The constitutive expression of either transgene did not alter the properties of hESCs in the culture," scientists in the United States report. "We next monitored the formation of teratomas in SCID mice to test (1) whether the gene-modified hESCs maintain their developmental pluripotency, and (2) whether sustained reporter gene expression allows noninvasive, whole-body imaging of hESC derivatives in a live mouse model. We observed teratoma formation from both types of gene-modified cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical imaging system, bioluminescence from the fLuc-transduced hESCs was easily detected in mice bearing teratomas long before palpable tumors could be detected. To develop a noninvasive imaging method more readily translatable to the clinic, we also utilized HSV1-TK and its specific substrate, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-[I-125]iodouracil ([I-125]FIAU), as a reporter/probe pair. After systemic administration, [I-125] FIAU is phosphorylated only by the transgene-encoded HSV1-TK enzyme and retained within transduced (and transplanted) cells, allowing sensitive and quantitative imaging by single-photon emission computed tomography," wrote M.G. Pomper and colleagues. The researchers concluded: "Noninvasive imaging methods such as these may enable us to monitor the presence and distribution of transplanted human stem cells repetitively within live recipients over a long term through the expression of a reporter gene.." Pomper and colleagues published their study in Cell Research (Serial imaging of human embryonic stem-cell engraftment and teratoma formation in live mouse models. Cell Research, 2009;19(3):370-379). For additional information, contact L.Z. Cheng, Johns Hopkins Institute Cell Engineering, 733 N Broadway, Broadway Research Bldg, Room 747, Baltimore, MD 21205, USA. The publisher's contact information for the journal Cell Research is: Nature Publishing Group, 75 Varick St., 9TH Flr, New York, NY 10013-1917, USA. Keywords: United States, Baltimore, Bioluminescence, Biotechnology, Embryonic Stem Cell Research, Enzyme Research, Enzymes, Enzymology, Gene Therapy, Genetics, Genomics, Kinase, Luciferase, Pharmaceuticals, Proteins, Proteomics, Reporter Gene, Severe Combined Immunodeficiency, Teratoma, Thymidine Kinase, Transplantation, Urology. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2009, Proteomics Weekly via NewsRx.com.
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