This is an exciting study to show in vivo migration of stem cells in the brain. I talked with the author at the Neuroscience meeting in Orlando, and was immediately impressed with their results. It shows dynamic migration of transplanted stem cells toward the lesion area, and such a pathway is exactly what we have expected based on the postmortem studies. I cannot wait to see how this technology advances clinical application of stem cell transplantation. We will be able to visualize real-time migration or distribution of transplanted cells in the live human brain.

Another group (Michel Modo et al., 2002), also published a similar technology, but they employed a slightly more elegant way, which is a combination of a MRI-enhancing molecule and a fluorescent dye molecule. This approach may be particularly useful for animal studies, where we may combine in vivo and postmortem analysis of the stem cell migration.

In any event, these technologies will become more powerful with the construction of...  Read more

This is an exciting study to show in vivo migration of stem cells in the brain. I talked with the author at the Neuroscience meeting in Orlando, and was immediately impressed with their results. It shows dynamic migration of transplanted stem cells toward the lesion area, and such a pathway is exactly what we have expected based on the postmortem studies. I cannot wait to see how this technology advances clinical application of stem cell transplantation. We will be able to visualize real-time migration or distribution of transplanted cells in the live human brain.

Another group (Michel Modo et al., 2002), also published a similar technology, but they employed a slightly more elegant way, which is a combination of a MRI-enhancing molecule and a fluorescent dye molecule. This approach may be particularly useful for animal studies, where we may combine in vivo and postmortem analysis of the stem cell migration.

In any event, these technologies will become more powerful with the construction of higher-resolution (tesla) MRI machines, and more important when we get closer to the clinical application of the neural stem cell transplantation.

View all comments by Kiminobu Sugaya

Stem cells have the potential to treat and possibly cure a variety of disorders, particularly those of the central nervous system. To develop successful clinical therapies, the fate of these cells after grafting must be monitored in a noninvasive manner. By incorporating magnetic nanoparticles or other MR contrast agents into stem and progenitor cells, it has previously been shown that MR imaging can detect the biodistribution of these cells.^(1-3) In the present paper, Hoehn and Küstermann et al. have taken this approach one step further and shown that the actual migration (i.e., movement) of transplanted mouse embryonic stem (ES) cells can be monitored in vivo. Mouse ES cells were magnetically labeled using a simple transfection method⁵ and transplanted in the contralateral hemisphere of rats two weeks after unilateral middle cerebral artery occlusion, an experimental model for stroke. They observed migration away from the implantation site along the corpus callosum toward the ischemic borderzone, mainly near the ventricular wall and choroid plexus. The...  Read more

Stem cells have the potential to treat and possibly cure a variety of disorders, particularly those of the central nervous system. To develop successful clinical therapies, the fate of these cells after grafting must be monitored in a noninvasive manner. By incorporating magnetic nanoparticles or other MR contrast agents into stem and progenitor cells, it has previously been shown that MR imaging can detect the biodistribution of these cells.^(1-3) In the present paper, Hoehn and Küstermann et al. have taken this approach one step further and shown that the actual migration (i.e., movement) of transplanted mouse embryonic stem (ES) cells can be monitored in vivo. Mouse ES cells were magnetically labeled using a simple transfection method⁵ and transplanted in the contralateral hemisphere of rats two weeks after unilateral middle cerebral artery occlusion, an experimental model for stroke. They observed migration away from the implantation site along the corpus callosum toward the ischemic borderzone, mainly near the ventricular wall and choroid plexus. The experimental high-field MR scanner used enabled a sufficiently high resolution to detect these structures, which corresponded to the immunospecific staining for transfected GFP used as a histopathological marker. However, it is, at present, uncertain if Hoehn’s approach will be indeed applicable to the use of standard clinical MR units to detect the migration of single clusters of magnetically labeled cells. Of further interest is that the transplanted mouse ES cells appeared to have morphologically differentiated into neurons, although further characterization data on the various possible cell lineages are pending. This study is a proof of principle of the great potential of MR imaging to follow cell migration, justifying further studies on its use in future clinical stem cell transplantation protocols.

References:
1. Bulte JWM, Zhang SC, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA. Neurotransplantation of magnetically labeled oligodendrocytes progenitors: MR tracking of cell migration and myelination. Proc Natl Acad Sci USA 1999;96:15256-15261.

2. Bulte JWM, Douglas T, Witer B, Zhang SC, Strable, E,Lewis B, Miller B, van Gelderen P, Moskowitz BM, Zywicke H, Duncan, ID, Frank JA. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells Nature Biotechnology 2001;19:1141-1147.

3. Modo M, Cash D, Mellodew K, Williams S, Fraser S, Meade T, Price J, Hodges H. Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging Neuroimage 2002;17:803-811.

4. Hoehn M, Küstermann E, Blunk J, Wiedermann D, Trapp T, Föcking M, Arnold H, Hescheler J, Fleischmann BK, Bührle C. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc. Natl. Acad. Sci. USA, in press.

5. Frank JA, Zywicke H, Jordan EK, Mitchell J, Lewis BK, Miller B, Bryant Jr. LH, Bulte JWM. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Academic Radiology 2002;9:S484-488.

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