Glenn Walter Assistant Professor Telephone: (352) 392-0551 Facsimile: (352) 846-0270 e-mail: glennw@phys.med.ufl.edu Web: http://www.med.ufl.edu/phys/ glennw.shtml

Laboratory Focus:

Common techniques to monitor muscle stem cell transplants typically rely on ex vivo genetic modification to allow expression of reporter genes. The statement of specific reporter genes allows for graft identification during post-mortem analysis. Using these conventional techniques, however, even simple and practical questions are difficult and labor intensive to answer. For example, to determine the distribution of the graft, the entire organ must be harvested and sectioned, followed by identification of individual cells by conventional microscopy. More complex questions, such as cell homing, identification of migration events, and engraftment rates, may be impossible to accurately and quantitatively address using conventional microscopy. Novel techniques that allow non-invasive, continuous imaging of stem cell transplants have recently been proposed and evaluated in a limited number of cell delivery models. We have previously found that magnetic resonance (MR) methods can be used to noninvasively monitor the widespread expression of a MR marker gene (arginine kinase; [1]) and therapeutic genes for the muscular dystrophies and cardiomyopathies [2]. On the other hand, cell based therapies represent a greater challenge for noninvasive monitoring due to the variability and limited stem cell incorporation. We found that MR imaging (MRI) has the ability to provide extremely sensitive, high-resolution images of magnetically labeled cells in both skeletal and cardiac muscle. As such, the application of MRI of stem cell investigations is of great importance to enhance the development of stem cell therapies. We have evaluated the application of magnetically labeled stem cells for the noninvasive monitoring of therapeutic stem cell transplants in murine dystrophies, senescent muscle, and cardiac dysfunction. Additional studies have revealed that MRI can be implemented to track the migration of a small number of labeled cells following arterial delivery to regions of targeted gene expression and tissue damage. These MR labeling strategies are not limited to muscle applications but can be readily extended to the noninvasive cell tracking in the brain, liver, and retina in both small animal models and humans.

Selected Publications:

Walter, G., E.R. Barton, and H.L. Sweeney
Noninvasive measurement of gene expression in skeletal muscle.
Proc Natl Acad Sci U S A, 2000. 97(10): p. 5151-5.

Fraites, T.J., Jr., et al.
Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors.
Mol Ther, 2002. 5(5 Pt 1): p. 571-8.

Walter NIH Biosketch