As stem cell science continues to heat up around the world, the need for non-invasive technologies to track implanted cells grows. MRI may well be the ideal technique for monitoring cells as it is high resolution, and unlike x-ray, electron or radionuclide based methods, is fundamentally non-ionizing. It is now common practice to introduce contrast agents into biological MRI specimens in order to make the differentiation of materials easier. Of these contrast agents (CAs) the most common type are the so-called T1-weighted CAs; paramagnetic particles which produce a bright contrast.
T1-weighted CAs based on Gd3+ are popular, thanks to the high magnetic moment of the Gd3+ ion. Although Gd is toxic it is safe to use in some chemical configurations, and several approved Gd CAs exist. Unfortunately the CAs currently available do not penetrate cells, and so only truly image the intermediate space. However, researchers based at Rice University and surrounding hospitals have developed nanotube capsules that contain gadolinium [Tran et al., (2010) Biomaterials 31, 9491]. These gadonanotubes (GNTs) are short segments (up to 80 nm) of single-walled carbon nanotubes which contain Gd3+ ions at defects along the interior wall.
The complete labeling of a cell batch took approximately four hours, after which time each cell contained 109 Gd3+ ions, in the most efficient case. This value then remained constant within a 24 hour window. The exact method of how the cells take-in the GNTs remains unclear, and is currently under investigation. Once the GNTs have been absorbed they appear to remain relatively stable inside the structure, being released upon cell death. However, the presence of the nanotubes does not seem to adversely affect cell behavior, as the cells are able to renew as well as differentiate into specific cell types.
The gadonanotubes provide a much greater contrast enhancement, compared to the commercially available CAs tested under identical labeling concentrations. However, there is still work to be done before GNTs are being used to monitor cells within living organisms, such as understanding how the GNTs affect cell adhesion. Nevertheless, the signs are positive, and the limiting factor for real time cell tracking may soon be the sensitivity of the local MRI machine.
Stewart Bland