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| Sun Oct 16, 2005 5:09 am updates on research |
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Progress in Research > Research Highlights Winter/Spring 2005
New Technology Tracks Cells in MS-like Disease
One of the oldest problems in biomedical research has been: How do you look inside a living body and observe cell activities without destroying the body? One key may be “cell-specific” imaging, a powerful tool that is helping MS researchers trace and observe destructive immune cells and even cells that may help repair MS damage. Cell-specific imaging works much like a microscopic Global Positioning System.
Tracking Immune T Cells
Moses Rodriguez, MD (Mayo Clinic and Foundation, Rochester, MN) and colleagues developed a cell-specific imaging technique in which they take antibodies (immune system proteins that target specific molecules) and tag them with tiny magnetic iron oxide particles. These antibodies are then injected into a laboratory animal where they find and bind to T cells. The iron particles become absorbed within the T cells. Using imaging, which detects iron, T cells that were bound by the specific antibody can thus be seen in living animals.
Rodriguez compared MRI images of tagged immune cells in animals with the MS-like disease EAE to actual tissue samples from the same animals in a pilot project funded by the National MS Society. He found that the areas where iron was detected in imaging corresponded precisely to areas where T cells infiltrated the nervous system, as seen in tissue samples (The FASEB Journal, January 2004).
In a related approach, Stasia Anderson, PhD, and colleagues (National Institutes of Health, Bethesda, MD) took T cells that induce the MS-like disease EAE, labeled them with iron oxide particles, and then injected them into mice. The iron-tagged T cells were detected via MRI within areas of myelin damage, and these findings correlated well with the location of T cells in tissue samples analyzed in the laboratory. Anderson comments that this technology may provide important information on the dynamics of T cell migration into the brain and spinal cord in MS, a key step in development of disease (Annals of Neurology, May 2004).
Tracing Repair Cells
Cell-specific imaging not only holds promise for observing the attack that damages MS, but also may help investigators someday deliver cell- or antibody-based therapies to treat MS.
Jeff Bulte, PhD (Johns Hopkins University, Baltimore) and colleagues studied nerve stem cells (immature cells capable of forming brain cells) in a pilot project funded in full by donors to the Society’s Maryland chapter. Bulte’s team labeled mouse nerve stem cells with tiny iron oxide particles, injected them into the brains of mice with EAE, and tracked them using MRI. Bulte found that the cells moved into areas of nerve damage, and that most movement or migration of the injected cells occurred early during active disease, and migration correlated with severity of disease (reported at the 2004 ACTRIMS meeting). The labeling substance used in this study is already approved by the FDA for use in humans.
In a landmark study, Gianvito Martino, MD (San Raffaele Hospital, Milan) and colleagues successfully injected adult mouse nerve stem cells to promote tissue repair and clinical recovery in EAE. With a grant from the Society, Martino is now “radiolabeling” the cells – tagging them with a mildly radioactive molecule – and injecting them into mice with EAE, in order to track the cells and determine what immune messenger proteins and other homing molecules are activated as cells migrate into the nervous system.
Schwann cells and olfactory ensheathing cells – myelin-making cells from nerves outside the brain and spinal cord – promote nerve fiber regeneration and myelin repair in mouse models of MS-like disease. Robin Franklin, PhD, DVM, and colleagues (University of Cambridge, UK) tagged these cells with iron oxide particles and then transplanted them into areas of myelin damage in the spinal cord in rats. Tagging allowed them to trace the cells, which retained their function and were able to form new myelin. Franklin’s team verified these results by examining the tissues microscopically. (The Journal of Neuroscience, November 3, 2004).
Rodriguez is also applying his imaging technique to track antibodies with repair potential, with funding from the Society’s Collaborative MS Research Center Award. He previously identified a human antibody called rHIgM22, which attaches to myelin-making cells and promotes myelin repair. Now Rodriguez and a multidisciplinary group of Mayo colleagues are exploring this molecule further. The team is using its imaging technology to track tagged rHIgM22 antibodies into areas of myelin damage. They recently reported more evidence that rHIgM22 promotes repair, probably by binding to cells in the nervous system (The FASEB Journal, October 2004).
Further research is needed to develop this technology for safe and practical use in persons with MS. Cell-specific imaging may increase our knowledge of the immune attack in MS exponentially, and may allow researchers to track, in future clinical trials, whether transplanted cells get where they are needed to restore function in people with M |
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