Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model

PLoS One. 2011;6(9):e22949. doi: 10.1371/journal.pone.0022949. Epub 2011 Sep 1.


The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arabinofuranosyluracil / analogs & derivatives
  • Cell Differentiation*
  • Cell Line
  • Cell Separation
  • Cell Survival
  • Disease Models, Animal
  • Echocardiography
  • Endothelial Cells / diagnostic imaging
  • Endothelial Cells / pathology
  • Feasibility Studies
  • Genes, Reporter / genetics
  • Herpesvirus 1, Human / enzymology
  • Lymph Nodes / pathology
  • Lymphatic Vessels / pathology
  • Lymphography
  • Magnetic Resonance Imaging
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / diagnostic imaging
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / surgery
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Positron-Emission Tomography*
  • Swine
  • Thymidine Kinase / genetics
  • Time Factors
  • Tomography, X-Ray Computed*


  • 2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-D-arabinofuranosyl uracil
  • Arabinofuranosyluracil
  • Thymidine Kinase