title: Multiparametric optical and MR imaging demonstrate inhibition of tumor angiogenesis natural history by mural cell therapy.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Treatment by MPC resulted in slowing down of tumor growth, capillary permeability decrease, and stabilization of tumor angiogenesis.
authors.affiliation: Université Paris Descartes Sorbonne Paris Cité, INSERM UMR-S970, Paris, France; CHRU Lille, Hôpital Jeanne de Flandre, Women medical imaging, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faye
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.forename: Daniel
authors.initials: D
authors.lastname: Balvay
authors.forename: Victor
authors.initials: V
authors.lastname: Fitoussi
authors.forename: Laetitia
authors.initials: L
authors.lastname: Pidial
authors.forename: Federico
authors.initials: F
authors.lastname: Sandoval
authors.forename: Gwennhael
authors.initials: G
authors.lastname: Autret
authors.forename: Jean Sébastien
authors.initials: JS
authors.lastname: Silvestre
authors.forename: Carole Leré
authors.initials: CL
authors.lastname: Dean
authors.forename: Marianne
authors.initials: M
authors.lastname: Alison
authors.forename: Laure S
authors.initials: LS
authors.lastname: Fournier
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005290:Ferric Compounds; D064593:Heterografts; D006801:Humans; D051379:Mice; D008833:Microcirculation; D018613:Microscopy, Confocal / Q000379:methods*; D053758:Nanoparticles; D013194:Staining and Labeling; D033581:Stem Cell Transplantation / Q000379:methods*; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D005290:Ferric Compounds
keywords: BOLD imaging; diffusion imaging; mural cells; optical imaging; tumor microcirculation