title: Magnetic resonance imaging of mesenchymal stem cells labeled with dual (MR and fluorescence) agents in rat spinal cord injury.
abstract: OBJECTIVE
  In vivo tracking cells using gadolinium-based contrast agents have the important advantage of providing a positive contrast on T1-weighted images, which is less likely to be confused with artifacts because of postoperative local signal voids such as metal, hemorrhage, or air. The aim of this study is to paramagnetically and fluorescently label marrow with dual agents (gadolinium-diethylene triamine penta-acetic acid [Gd-DTPA] and PEI-FluoR) and track them after transplantation into spinal cord injury (SCI) with magnetic resonance imaging (MRI).
  
  
  METHODS
  Marrow mesenchymal stem cells (MSCs) from Sprague-Dawley rats were incubated with PEI-FluoR (rhodamine-conjugated PEI-FluoR) and Gd-DTPA complex for labeling. After labeling, cellular viability, proliferation, and apoptosis were evaluated. T1 value and longevity of intracellular Gd-DTPA retention were measured on a 1.5 T MRI scanner. Thirty-six SCI rats were implanted with labeled and unlabeled MSCs and phosphate-buffered saline. Then, serial MRI and Basso-Beattie-Bresnehan (BBB) locomotor tests were performed and correlated with fluorescent microscopy. The relative signal intensity (RSL) of the engraftment in relation to normal cord was measured and the linear mixed model followed by post-hoc Bonferroni test was used to identify significant differences in RSL as well as BBB score.
  
  
  RESULTS
  MSCs could be paramagnetically and fluorescently labeled by the dual agents. The labeling did not influence the cellular viability, proliferation, and apoptosis. The longevity of Gd-DTPA retention in labeled MSCs was up to 21 days. The distribution and migration of labeled MSCs in SCI lesions could be tracked until 7 days after implantation on MRI. The relative signal intensities of SCI rats treated with labeled cells at 1 day and 3 days (1.34 +/- 0.02, 1.27 +/- 0.03) were significantly higher than rats treated with unlabeled cells (0.94 +/- 0.01, 0.99 +/- 0.02) and phosphate-buffered saline (0.91 +/- 0.01, 0.95 +/- 0.01) (P < .05). Rats treated with labeled MSCs or unlabeled MSCs achieved significantly higher BBB scores than controls at 14, 21, 28, and 35 days after injury (P < .05).
  
  
  CONCLUSIONS
  Labeling MSCs with the dual agents may enable cellular MRI and tracking in experimental spinal cord injury.
authors: Department of Radiology, The Second Affiliated Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China. junshenjun@hotmail.com
authors: Jun
authors: J
authors: Shen
authors: Xiao-Mei
authors: XM
authors: Zhong
authors: Xiao-Hui
authors: XH
authors: Duan
authors: Li-Na
authors: LN
authors: Cheng
authors: Guo-bing
authors: GB
authors: Hong
authors: Xiao-Bing
authors: XB
authors: Bi
authors: Yu
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008856:Microscopy, Fluorescence / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000601:surgery*; D013194:Staining and Labeling / Q000379:methods; D025321:Surgery, Computer-Assisted / Q000379:methods*