Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction.
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.
Wisenberg
Gerald
G
Department of Medicine, University of Western Ontario, Ontario, Canada. gerald.wisenberg@lawsonimaging.ca
Lekx
Katie
K
Zabel
Pam
P
Kong
Huafu
H
Mann
Rupinder
R
Zeman
Peter R
PR
Datta
Sudip
S
Culshaw
Caroline N
CN
Merrifield
Peter
P
Bureau
Yves
Y
Wells
Glenn
G
Sykes
Jane
J
Prato
Frank S
FS
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
D007205:Indium Radioisotopes; D009930:Organic Chemicals; C070080:PKH 26