Research

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

Gerald Wisenberg¹ , Katie Lekx² , Pam Zabel² , Huafu Kong² , Rupinder Mann² , Peter R Zeman¹ , Sudip Datta¹ , Caroline N Culshaw³ , Peter Merrifield³ , Yves Bureau² , Glenn Wells⁴ , Jane Sykes² and Frank S Prato²

¹  Department of Medicine, University of Western Ontario, Ontario, Canada

²  Department of Medical Biophysics, University of Western Ontario, Ontario, Canada

³  Department of Anatomy and Cell Biology, University of Western Ontario, Ontario, Canada

⁴  Department of Medicine, University of Ottawa, Ontario, Canada

author email corresponding author email

Journal of Cardiovascular Magnetic Resonance 2009, 11:11doi:10.1186/1532-429X-11-11

Published:	27 April 2009

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.

Objectives

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.

Conclusion

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.