Cell Tracking and Therapy Evaluation of Bone Marrow Monocytes and Stromal Cells Using SPECT and CMR in a Canine Model of Myocardial Infarction

Authors

Gerald Wisenberg, University of Western OntarioFollow
Katie Lekx, University of Western Ontario
Pam Zabel, University of Western OntarioFollow
Huafu Kong, University of Western Ontario
Rupinder Mann, University of Western Ontario
Peter R. Zeman, University of Western Ontario
Sudip Datta, University of Western OntarioFollow
Caroline N. Culshaw, University of Western Ontario
Peter Merrifield, University of Western OntarioFollow
Yves Bureau, University of Western OntarioFollow
Glenn Wells, University of Ottawa
Jane Sykes, University of Western Ontario
Frank S. Prato, University of Western OntarioFollow

Document Type

Article

Publication Date

4-27-2009

Journal

Journal of Cardiovascular Magnetic Resonance

Volume

11

Issue

11

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.

Notes

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