title: Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction.
abstract: BACKGROUND
  The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu.
  
  
  OBJECTIVE
  To establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling.
  
  
  METHODS
  We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells.
  
  
  RESULTS
  In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67-88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment.
  
  
  CONCLUSIONS
  This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.
authors.affiliation: Department of Medicine, University of Western Ontario, Ontario, Canada. gerald.wisenberg@lawsonimaging.ca
authors.forename: Gerald
authors.initials: G
authors.lastname: Wisenberg
authors.forename: Katie
authors.initials: K
authors.lastname: Lekx
authors.forename: Pam
authors.initials: P
authors.lastname: Zabel
authors.forename: Huafu
authors.initials: H
authors.lastname: Kong
authors.forename: Rupinder
authors.initials: R
authors.lastname: Mann
authors.forename: Peter R
authors.initials: PR
authors.lastname: Zeman
authors.forename: Sudip
authors.initials: S
authors.lastname: Datta
authors.forename: Caroline N
authors.initials: CN
authors.lastname: Culshaw
authors.forename: Peter
authors.initials: P
authors.lastname: Merrifield
authors.forename: Yves
authors.initials: Y
authors.lastname: Bureau
authors.forename: Glenn
authors.initials: G
authors.lastname: Wells
authors.forename: Jane
authors.initials: J
authors.lastname: Sykes
authors.forename: Frank S
authors.initials: FS
authors.lastname: Prato
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D004285:Dogs; D005260:Female; D007091:Image Processing, Computer-Assisted; D007205:Indium Radioisotopes; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D009000:Monocytes / Q000637:transplantation; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000601:surgery*; D009930:Organic Chemicals / Q000494:pharmacology; D017154:Stromal Cells / Q000637:transplantation; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D007205:Indium Radioisotopes; D009930:Organic Chemicals; C070080:PKH 26