Tamir Ben-Hur MD, Abstract Co-Author: Nothing to Disclose

Ruud van Heeswijk BS, Abstract Co-Author: Nothing to Disclose

Ofira Einstein BS, Abstract Co-Author: Nothing to Disclose

Michal Aharonovitch BS, Abstract Co-Author: Nothing to Disclose

Emma Frost, Abstract Co-Author: Nothing to Disclose

Jeff W.M. Bulte PhD, Presenter: Nothing to Disclose

In order to guide the development of new stem cell-based therapies for the treatment of multiple sclerosis, we applied serial MR imaging to assess the speed and preferred routes of migration of labeled stem cell transplants in a chronic EAE mouse model.

Mouse and human neural stem cells were labeled with PLL-Feridex, while using BrdU or GFP as histological validation marker. Chronic EAE was induced in C57Bl/6 mice using a standard MOG immunization protocol, and mice were assigned a daily score for neurological symptoms. Cells were transplanted in both lateral ventricles on day 6 following EAE induction (n=20). At days 1-2, 6-7, 13-14 and 30 after transplantation, serial MRI was performed using a 4.7 Tesla system and a 3D RARE sequence with 50-78 mm resolution. The distance of migration was calculated from the MR slices, starting at the ventricular edge to the most distant site of hypointense signal. MR data were validated by comparing the distribution of BrdU+ or GFP+ cells to that of Prussian blue (iron) stainings.

At days 1-2 after transplantation, the grafts were located mainly in the lateral ventricles. As early as 6 days after transplantation, hypointense MRI signals were observed in white matter tracts. These were further observed on images taken at days 13-14 and 30 post transplantation. Migration was most commonly observed in the corpus callosum and internal capsule towards the cerebral peduncles and in the stria-medullaris and fornix. MRI measurements indicated that most of the migration occurred within the first 2 weeks, during the acute phase of disease. As compared to the mouse cells, the human cells migrated slower and to a shorter distance. The variance in clinical scores and distance of migration demonstrated a good correlation between disease severity and extent of migration.

The greatest degree of stem cell migration occurs very early in the course of disease, emphasizing a narrow time window for transplantation protocols aimed at obtaining clinical results. The MRI results demonstrate that inflammatory signals associated with the clinical score can modulate stem cell migration in a positive manner.Supported by RO1 NS045062 and NMSS PP0922.

Ben-Hur, T, van Heeswijk, R, Einstein, O, Aharonovitch, M, Frost, E, Bulte, J, Serial MR Imaging of Stem Cell Migration in a Mouse Model of Multiple Sclerosis.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4415832.html