title: In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging (MEMRI).
abstract: BACKGROUND
  Transplantation of mononuclear cells (MNCs) has previously been tested as a method to induce therapeutic angiogenesis to treat limb ischemia in clinical trials. Non-invasive high resolution imaging is required to track the cells and evaluate clinical relevance after cell transplantation. The hypothesis that MRI can provide in vivo detection and long-term observation of MNCs labeled with manganese contrast-agent was investigated in ischemic rat legs.
  
  
  RESULTS
  The Mn-labeled MNCs were evaluated using 7-tesla high-field magnetic resonance imaging (MRI). Intramuscular transplanted Mn-labeled MNCs were visualized with MRI for at least 7 and up to 21 days after transplantation in the ischemic leg. The distribution of Mn-labeled MNCs was similar to that of ¹¹¹In-labeled MNCs measured with single-photon emission computed tomography (SPECT) and DiI-dyed MNCs with fluorescence microscopy. In addition, at 1-2 days after transplantation the volume of the site injected with intact Mn-labeled MNCs was significantly larger than that injected with dead MNCs, although the dead Mn-labeled MNCs were also found for approximately 2 weeks in the ischemic legs. The area covered by CD31-positive cells (as a marker of capillary endothelial cells) in the intact Mn-MNCs implanted site at 43 days was significantly larger than that at a site implanted with dead Mn-MNCs.
  
  
  CONCLUSIONS
  The present Mn-enhanced MRI method enabled visualization of the transplanted area with a 150-175 µm in-plane spatial resolution and allowed the migration of labeled-MNCs to be observed for long periods in the same subject. After further optimization, MRI-based Mn-enhanced cell-tracking could be a useful technique for evaluation of cell therapy both in research and clinical applications.
authors: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors: Kenichi
authors: K
authors: Odaka
authors: Ichio
authors: I
authors: Aoki
authors: Junji
authors: J
authors: Moriya
authors: Kaoru
authors: K
authors: Tateno
authors: Hiroyuki
authors: H
authors: Tadokoro
authors: Jeff
authors: J
authors: Kershaw
authors: Tohru
authors: T
authors: Minamino
authors: Toshiaki
authors: T
authors: Irie
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Issei
authors: I
authors: Komuro
authors: Tsuneo
authors: T
authors: Saga
mesh_terms: D000818:Animals; D001775:Blood Circulation; D001854:Bone Marrow Cells / Q000166:cytology*; D058948:Cell Tracking / Q000379:methods*; D017690:Cell Transplantation; D002712:Chlorides / Q000378:metabolism; D003287:Contrast Media / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007700:Kinetics; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D009942:Organometallic Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C032950:indium oxine; D015125:Oxyquinoline; C025340:manganese chloride