Tracking cellular regeneration
In recent years, stem cells have shown a great potential in regenerative medicine. However, a greater understanding in mechanism, function, and distribution of stem cells used for cellular regeneration in vivo is strongly needed. To investigate stem cell activities in vivo, labeling and tracking stem cells with metallic nanoparticles are quite attractive techniques. As mentioned previously, metallic nanoparticles have excellent physical and chemical properties, especially their optical property that supports metallic nanoparticles for use in various imaging systems. For example, rod-shaped gold nanoparticles (gold nanorods, GNRs) were coated with silica and used as a photoacoustic contrast agent to track stem cells in the musculature of riving mice. After an injection of mesenchymal stem cells labeled with silica-coated GNRs, the labeled mesenchymal stem cells were detected in mice after photoacoustic rmaging (Jokerst et al., 2012). The monitoring of skin tissue construction of adipose-derived stem cells (ASCs) labeled with PEGylated GNRs that coated a silica layer was also performed by Nam et al. (2015). With this technique, they could detect ASCs in the burn tissue of rats. The former work carried out by Nam et al. (2012) also labeled mesenchymal stem cells with 20 nm GNPs (citrate reduction gold nanospheres). The signal from the optical absorption of GNP labeling on mesenchymal stem cells could be monitored and tracked in Lewis rats using ultrasound-guided spectroscopic imaging and photoacoustic imaging. After GNPs were intramuscularly injected to rats, mesenchymal stem cell monitoring was detected through the spatial distribution of labeled cells for 3, 7, and 10 days (Fig. 7.3). It is worth noting here that GNPs used in their study were contained in a PEGylated fibrin gel system.
Figure 7.3 Monitoring of mesenchymal stem cells labeled with GNPs (a, shown in green) using ultrasound-guided spectroscopic imaging at 3, 7, and 10 days. The photoacoustic signals of mesenchymal stem cells labeled with GNPs (b). GNPs, gold nanoparticles.
Reproduced with permission from Nam, S.Y., Ricles, L.M., Suggs, L.J., Emelianov, S.Y., 2012. In vivo ultrasound and photoacoustic monitoring of mesenchymal stem cells labeled with gold nanotracers. PLoS One 7, e37267.
Magnetic resonance imaging (MRI) is another technique that can be used to monitor and assess cell activities and cell conditions. Cho et al. (2014) prepared iron oxide nanocrystals combined with bacterial genes, referred to as MagA, to monitor stem cell grafts in mice induced by doxycycline through diet (Tet-On; tetracycline inducible gene expression). This MagA acted as a genetic MRI reporter that could control the level of MRI contrast and also assess the cell grafts used for regenerative medicine. The tracking of mesenchymal stem cells labeled with chitosan-superparamagnetic iron oxide nanoparticles in rabbit brains under MRI was also performed by Reddy et al. (2010). Superparamagnetic iron oxide nanoparticles labeled with mesenchymal stem cells were also used to track how mesenchymal stem cells could be involved in the treatment of rheumatoid arthritis in vivo. With MRI, this technique can help gain information on mesenchymal stem cell mechanisms such as cell migration, cell localization, and rate of tissue repair by tracking stem cells (Markides et al., 2013).