Neuroscience 2005 Abstract
| Presentation Number: | 816.14 |
|---|---|
| Abstract Title: | Validity of magnetic resonance imaging in monitoring cell therapy for myelin disease. |
| Authors: |
Walczak, P.*1
; Kedziorek, D. A.1
; Gilad, A. A.1
; Lin, S.1
; Bulte, J. W. M.1
1Radiology, Johns Hopkins Univ., Baltimore, MD |
| Primary Theme and Topics |
Techniques in Neuroscience - Staining, Tracing, and Imaging Techniques |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Demyelinating Disorders<br />-- Molecular and cellular mechanisms |
| Session: |
816. Imaging by MRI and PET III Slide |
| Presentation Time: | Wednesday, November 16, 2005 11:15 AM-11:30 AM |
| Location: | Washington Convention Center - Room 149A |
| Keywords: | MRI CELL TRACKING, STEM CELL, TRANSPLANTATION, MYELINATION |
The utilization of stem cells as therapeutic agents is an active area of current research. Although cell-based therapy has been successfully implemented in animal models of stroke or Parkinson’s disease, clinical trials have demonstrated only modest therapeutic effects. Further research is needed to better understand the mechanisms governing cellular migration and differentiation. Magnetic resonance (MR) tracking of stem cells is a new emerging application that aims to obtain a better understanding of the dynamics of cell-tissue interactions, as well as to aid in guiding the development of effective cell therapies.
In this study we report on the applicability of MR tracking of magnetically labeled (magnetofected) neural stem cells following transplantation into the dysmyelinated mouse brain. LacZ-transfected C17.2 neural stem cells were Feridex/poly-L-lysine labeled and transplanted into the lateral ventricle of neonatal shiverer mice. In vivo MR imaging was performed at 1, 4, 7 and 14 days after cell transplantation. To validate MR data and confirm the distribution of transplanted cells, 1-60 days post-transplantation brains were processed for b-galactosidase, dextran immunohistochemistry, and Prussian blue staining for iron. New myelination was assessed with antibody against myelin basic protein. MR imaging at early time points (1-4 days) revealed iron-induced MR signal loss throughout the entire ventricular system reaching the central canal of spinal cord. These findings were in good agreement with histological detection. At later time points the migration of transplanted cells was extensive, however, this pattern only correlated partly with the MRI findings. This discordance was found to result from multiple cell divisions, significantly diluting the contrast agent. Ongoing experiments will address myelinization potential of both magnetofected and unlabeled stem cells. We conclude that MR imaging is useful for early non-invasive monitoring of transplanted stem cells, but should be considered unreliable for rapidly proliferating cells at later time points.
In this study we report on the applicability of MR tracking of magnetically labeled (magnetofected) neural stem cells following transplantation into the dysmyelinated mouse brain. LacZ-transfected C17.2 neural stem cells were Feridex/poly-L-lysine labeled and transplanted into the lateral ventricle of neonatal shiverer mice. In vivo MR imaging was performed at 1, 4, 7 and 14 days after cell transplantation. To validate MR data and confirm the distribution of transplanted cells, 1-60 days post-transplantation brains were processed for b-galactosidase, dextran immunohistochemistry, and Prussian blue staining for iron. New myelination was assessed with antibody against myelin basic protein. MR imaging at early time points (1-4 days) revealed iron-induced MR signal loss throughout the entire ventricular system reaching the central canal of spinal cord. These findings were in good agreement with histological detection. At later time points the migration of transplanted cells was extensive, however, this pattern only correlated partly with the MRI findings. This discordance was found to result from multiple cell divisions, significantly diluting the contrast agent. Ongoing experiments will address myelinization potential of both magnetofected and unlabeled stem cells. We conclude that MR imaging is useful for early non-invasive monitoring of transplanted stem cells, but should be considered unreliable for rapidly proliferating cells at later time points.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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