Multiparametric optical and MR imaging demonstrate inhibition of tumor angiogenesis natural history by mural cell therapy.

ABSTRACT

PURPOSE: To determine whether functional imaging using MRI and fibered confocal fluorescence microscopy (FCFM) could be used to monitor cell therapy by mural progenitor cells (MPC). METHODS: Fifty mice bearing TC1 murine xenograft tumors were allocated into control (n = 17), sham (phosphate buffer saline, n = 16), and MPC-treated (MPC, n = 17) groups. MRI was performed before (D0 ) and 7 days (D7 ) after injection measuring tumor size, R2 * under air, oxygen, and carbogen using blood oxygen level dependent (BOLD) and f (fraction linked to microcirculation), D* (perfusion related coefficient) and Dr (restricted diffusion coefficient) using diffusion-weighted sequences based on the IVIM (intravoxel incoherent motion) method. FCFM was performed at D7 measuring "index leakage" (capillary permeability). RESULTS: Tumor growth was significantly slowed down in the MPC-treated animals (P = 0.002) on D7 . R2 *air significantly decreased in controls between D0 and D7 (P = 0.03), reflecting a decrease in tumor oxygenation. ΔR2 *O2CO2 significantly increased in controls between D0 and D7 (P = 0.01) reflecting loss of vessel response to carbogen. D* significantly decreased in controls between D0 and D7 (P = 0.03). Finally, "index leakage" was lower in the MPC-treated tumors (P = 0,009). CONCLUSION: Treatment by MPC resulted in slowing down of tumor growth, capillary permeability decrease, and stabilization of tumor angiogenesis.