Figure 7.

Intravenously-delivered superparamagnetic iron oxide (SPIO) NP-loaded MSCs localize to lung metastases and can be visualized by MRI. (A) Representative coronal MRI sections (n = 4 mice) of a normal mouse lung (Normal), mouse lung with metastases 35 d after i.v. delivery of MDAMB231 cells (pre-MSC), and the same mouse lung 1 h after SPIO-loaded MSC injection (post-MSC). The metastases (circled) are visualized as focal regions of increased signal. These areas correspond to metastases on H&E histologic sections (bar, 100 μm). One hour after SPIO-loaded MSC injection, there is a decrease in signal intensity caused by the iron oxide in MSCs (+, ribcage; *, trachea; ^, diaphragm with upper abdomen below; ~, fissure separating lobes). (B) The reduction in signal intensity secondary to the NP-loaded MSCs 1 and 24 h after MSC injection was further confirmed and quantified by comparing signal-to-noise ratio (SNR) between the lung parenchyma and the deltoid muscle in three consecutive MR slices in three mice; there was a significant (P = 0.005) reduction in SNR across all four radiological areas [left upper (LU), left lower (LL), right upper (RU), and right lower (RL)]. (C) Tumor histology from mice harvested at day 35, 1 h after NP-loaded MSC injection and MRI. Prussian blue (i) and DiI staining (ii; red) on contiguous sections from mice, showing that MSCs migrate to and incorporate into lung metastases after i.v. delivery (bar, 20 μm). iii, macrophage immunohistochemistry (brown) stains different cells from NP-loaded cells (blue stain). iv, macrophage immunofluorescence (green) stains different cells from DiI-labeled (red) cells (bar, 5 μm). Reproduced with permission.^[164] Copyright 2009 American Association for Cancer Research.