| Abstract No.: | C-F3176 |
| Country: | Canada |
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| Title: | IN VIVO TRACKING OF MESENCHYMAL STEM CELLS IN THE INJURED MOUSE SPINAL CORD. |
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| Authors/Affiliations: | 1 Laura Gonzalez-Lara*; 1 Xiaoyun Xu; 1 Klara Hofstetrova; 1 Soha Ramadan; 1 Nicole Geremia; 1 Anna Pniak; 1 Yuhua Chen; 1 Lynne Weaver; 1 Arthur Brown;
1 Robarts Research Institute, London, ON, Canada
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| Content: | Objectives: Recent reports show that mesenchymal stem cells (MSCs) can be induced to differentiate into neural cells.1,2 This makes them a promising option for nerve regeneration following a spinal cord injury (SCI). Magnetic resonance imaging (MRI) provides the opportunity to track MSCs transplanted into an injured spinal cord. However, in vivo imaging of the mouse spinal cord is extremely difficult because of the extreme curvature and size of the cord. In fact, there are no published reports of the use of in vivo MRI to monitor transplanted cells in models of mouse SCI. Our objectives were:
-To image the mouse spinal cord in vivo using a 3T clinical whole-body MR system
-To detect and monitor the lesion in the mouse spinal cord caused by a traumatic injury
-To monitor transplanted MSCs over time
We have implemented and optimized the microimaging technology to achieve these objectives.
Materials and Methods: MRI was performed using a specialized microimaging system on a clinical 3T GE MR scanner. Mice were placed in a custom-built sled to permit careful and reproducible positioning for sagittal imaging of the cord. Image resolution was 200x200x200 microns and image acquisition time was 31 min. MSCs were isolated from EGFP+ mice (Tg(ACTbEGFP)10sb) and labeled with magnetic beads (SiMAG, 0.75μm; chemicell, Berlin, Germany). A clip compression SCI was induced in genetically matched mice (K15-EGFP) at the level of the 4th thoracic vertebrae. An intraspinal transplant of MSCs was performed 48 hrs after the SCI (n=16); 13 mice received iron-labeled MSCs, 3 received unlabeled MSCs. Mice were imaged at 2 days post transplant and then weekly for up to 4-6 weeks.
Results: Excellent 3DFIESTA mouse cord images were obtained. The epicenter of the SCI was visible as a region of heterogeneous signal. The appearance of the injury changed over time; at 2 weeks post transplant small areas of hypointensity could be observed, due to the pathology, which were not always obvious at 2 days or 1 week post-transplant. Surprisingly, fluid filled cysts were sometimes observed rostral to the epicenter.
MSCs in mice that received iron-labeled cells appear as large, obvious regions of signal hypointensity in the cord. The region of signal loss caused by the presence of labeled MSCs diminished over time.
Conclusion: To the best of our knowledge, this is the first study that shows the use in vivo stem cell tracking in a mouse model of SCI. Challenges overcome to generate high quality images of the mouse cord in vivo included the small size, extreme curvature, respiratory motion and life support. Key to our success is the implementation of a fast 3D imaging sequence which is extremely sensitive to iron and has very high signal efficiency, together with the use of customized imaging hardware which permitted the acquisition of very high resolution images at clinical field strengths.
1. Tropel, et al. Stem Cells 2006, 24(12).
2. Jackson, et al. J Postgrad Med 2007, 53(2). |
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