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How to track a stem cell

Before therapies using human embryonic stem cells can be approved by the Food and Drug Administration, researchers will have to answer one key question: where do the cells go when they are injected into the patient? During an FDA meeting earlier this linkurl:month;http://www.the-scientist.com/templates/trackable/display/blog.jsp?type=blog&o_url=blog/display/54544&id=54544 on the safety of embryonic stem cell therapies, the agency grappled with the issues of tracking stem cells in vivo. Regardl

By | May 1, 2008

Before therapies using human embryonic stem cells can be approved by the Food and Drug Administration, researchers will have to answer one key question: where do the cells go when they are injected into the patient? During an FDA meeting earlier this linkurl:month;http://www.the-scientist.com/templates/trackable/display/blog.jsp?type=blog&o_url=blog/display/54544&id=54544 on the safety of embryonic stem cell therapies, the agency grappled with the issues of tracking stem cells in vivo. Regardless of whether stem cells need to target a specific location, such as the eye, or circulate the body, researchers need standardized tools to watch where the cells go and how they differentiate. But some experts wonder what the priorities should be in developing stem cell therapies. At the FDA meeting, linkurl:Kenneth Chien,;http://www.hms.harvard.edu/dms/bbs/fac/Chien.html from Harvard Medical School, asked whether new stem cell tracking technologies that are so far away are worth investing time and money in. I called up linkurl:Jeffrey Bulte;http://mri.kennedykrieger.org/sitemap/jbulte.html from Johns Hopkins University, who gave a presentation on the subject at the FDA meeting, and asked him to give a run down of tools his group is developing. First, a clinically approved radiolabeling agent for immune response and inflammation, called Indium Oxine, can be used to track embryonic stem cells. In linkurl:2005,;http://www.ncbi.nlm.nih.gov/pubmed/16129797?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Bulte and colleagues used Indium Oxine to watch canine bone marrow-derived mesenchymal stem cells disperse to other linkurl:organs;http://www.the-scientist.com/supplementary/html/24104/ after being injected into the blood. Using a specialized CT scanner, the researchers could see "hot spots" of the cells in the heart, liver, and kidney, Bulte told The Scientist. Bulte and other researchers are also developing reporter genes that are inserted into a stem cell's genome. These genes contain luciferase, the enzyme that makes fireflies glow; it lights up in living cells, and researchers can image the marker in small animals. But the much larger human body absorbs the light, so the technique won't work in the clinic. Also, reporter genes genetically alter cells, so there is a risk of side effects -- most importantly, altered cells are no longer stem cells and may behave differently than the population of stem cells as a whole. "The Holy Grail would be an MRI reporter gene" that provides MRI contrast in stem cells, Bulte said in his talk at the FDA meeting. Bulte's team is also developing capsules for tracking cells. "We encapsulate cells, put them in protective housing, label these capsules, and inject them," he said. "And using MRI we can see where they go." This technique allows the cell material to be protected and also released in a controlled way. But MRI isn't sensitive enough to track cells efficiently with these techniques. In collaboration with Philips Research in Hamburg, Bulte is developing a new imaging tool called magnetic particle imaging (MPI), which flips the magnetic field around a tissue sample back and forth and captures images as magnetically-treated cells give off a frequency. MPI is more sensitive to cell numbers than MRI and does not pick up the surrounding tissue, as does MRI, Butte said, but the technology may not be implemented for many years to come. He plans to present the concept and initial results at the annual meeting of the International Society of Magnetic Resonance in Toronto next week.
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