Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction

• Main Authors: Merrifield Peter, Culshaw Caroline N, Datta Sudip, Zeman Peter R, Mann Rupinder, Kong Huafu, Zabel Pam, Lekx Katie, Wisenberg Gerald, Bureau Yves, Wells Glenn, Sykes Jane, Prato Frank S
• Format: Article
• Language: English
• Published: BMC 2009-04-01
• Series: Journal of Cardiovascular Magnetic Resonance
• Online Access: http://www.jcmr-online.com/content/11/1/11
• ISSN: 1097-6647; 1532-429X

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Objectives</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>