|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, 1 January 2005, Vol. 105, No. 1, pp. 7-8.
Noninvasive monitoring of cellular movements: the utility of MRI and magnetically labeled cellsMASSACHUSETTS GENERAL HOSPITAL
Since the demonstration that stem cells can track to various regions within the body and differentiate in a site-specific manner, researchers have sought to exploit them for therapy. In this issue, Anderson and colleagues use MRI to monitor the migration of these "therapeutic cells" to the neovasculature in a glioma tumor model.
To move cellular transplantation therapy into the clinics, however, many aspects of the therapy need to be better elucidated. It is important to understand the temporal and spatial distribution of cells expressing a toxic or therapeutic gene product and to monitor the safety of transplants in patients. Traditional histologic analysis does not adequately address the dynamic nature of transplantation therapy creating a need for noninvasive technologies to assess the efficacy of cell transplantation in living animals in real-time. Noninvasive imaging will allow real-time monitoring of the survival, migration, and therapeutic and nontherapeutic consequences of transplanted cells.
In this issue of Blood, Anderson and colleagues have used magnetic resonance imaging (MRI) to follow magnetically labeled transplanted cells. In the reported studies, Sca1+ endothelial progenitor cells were labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and then injected into the vasculature of animals. In mice with orthotopically implanted gliomas, the labeled cells tracked to the tumor periphery and were initially visible by MRI as a slight darkening surrounding the tumor 9 days after implantation. At later time points, the darkening became more pronounced and progressed to a significant hypointense ring surrounding the tumor. Ex vivo high-resolution MRI (see figure) showed that labeled cells were also infiltrating into the interior of the tumors. In temporal studies, histology demonstrated that MR signals were present only when tumors were undergoing neovascular growth, and immunohisotchemistry confirmed that iron-containing cells within the tumor and its periphery were positive for 2 endothelial cell markers, CD-31 and von Willebrand factor. Although the study did not control for the potential leakage of iron from the transplanted cells and subsequent redistribution to vasculature, there are significant data from other studies to strongly suggest that this is not the mechanism in place.3 Furthermore, the use of labeled nonviable cells for control animals supports the authors' conclusions that ex vivo–labeled progenitor cells migrate and differentiate into endothelial cells and are responsible for the signal changes observed. Others have certainly demonstrated the use of various imaging modalities including MRI to track the migration of cells in vivo.4 However, the results of Anderson et al are very exciting because they are the first to demonstrate the utility of the approach for tracking the migration and differentiation of endothelial progenitor cells into tumor vasculature. In contrast to other noninvasive techniques used to assess microvessel density (e.g., perfusion imaging), this technology allows not only assessment of neovasculature but also the ability to noninvasively visualize functioning, genetically altered cells with resolution not obtainable by any other modality. As science moves toward more novel approaches for delivering genes to target tissues, clinical trials will require a means to assess dosage and frequency of cell transplants in order to optimize therapy and predict outcome and side effects. Approaches such as those described by Anderson et al will be important in helping to assess these parameters in vivo. References
  CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
