Abstract 351: In-vivo Stem Cell Tracking Using Ultrasound Imaging
Background: Exogenous delivery of reparative cells is a promising new approach to treating cardiovascular disease. Clinical application of cell therapies is limited by a lack of imaging methods for safely and serially tracking the fate of delivered cells in vivo. We recently showed that polymer microbubbles (MB) are internalized by mesenchymal stem cells (MSC), and that the MB-labeled MSCs (MB-MSC) have harmonic responses to ultrasound (US) and can be US imaged in vitro. We tested the hypothesis that MB-MSCs can be serially imaged in vivo with US.
Methods: Cultured human marrow-derived MSCs were exposed to biocompatible polymer MB (diameter 2.4±0.9μm) in a 1000 to 1 MB:MSC ratio for 12 hrs, washed, trypsinized, and re-suspended in culture medium. MB internalization was confirmed by microscopy and 2D US imaging. Nude mice (n=7) received 1.8 × 106 MSCs injected into hindlimb muscle (control); the same number of MB-MSCs was injected in the contralateral muscle. Non-linear US imaging of each hindlimb was performed at baseline and immediately and 4 hrs post injection. Videointensity (VI) in the muscle, expressed in dB, was measured.
Results: VI change was higher immediately after injection of MB-MSC (8±1 dB) vs MSCs only (3±2 dB, p<0.02) (Figure⇓). 4 hrs later, VI change in MB-MSC treated muscle remained higher vs control muscle (5±4 dB vs 2±2 dB, p≤0.04). In vitro viability and migration studies of MB-MSC up to 72 hr post labeling showed no change vs. MSCs alone.
Conclusions: MB-MSCs are acoustically active in vivo, and can be serially imaged with US up to at least 4 hours after injection. MBs can be useful stem cell imaging probes, and US may enable serial non-invasive spatial localization of MSC fate.