Targeting chronic cardiac remodeling with cardiac progenitor cells in a murine model of ischemia/reperfusion injury.
BACKGROUND
Translational failure for cardiovascular disease is a substantial problem involving both high research costs and an ongoing lack of novel treatment modalities. Despite the progress already made, cell therapy for chronic heart failure in the clinical setting is still hampered by poor translation. We used a murine model of chronic ischemia/reperfusion injury to examine the effect of minimally invasive application of cardiac progenitor cells (CPC) in cardiac remodeling and to improve clinical translation.


METHODS
28 days after the induction of I/R injury, mice were randomized to receive either CPC (0.5 million) or vehicle by echo-guided intra-myocardial injection. To determine retention, CPC were localized in vivo by bioluminescence imaging (BLI) two days after injection. Cardiac function was assessed by 3D echocardiography and speckle tracking analysis to quantify left ventricular geometry and regional myocardial deformation.


RESULTS
BLI demonstrated successful injection of CPC (18/23), which were mainly located along the needle track in the anterior/septal wall. Although CPC treatment did not result in overall restoration of cardiac function, a relative preservation of the left ventricular end-diastolic volume was observed at 4 weeks follow-up compared to vehicle control (+5.3 ± 2.1 μl vs. +10.8 ± 1.5 μl). This difference was reflected in an increased strain rate (+16%) in CPC treated mice.


CONCLUSIONS
CPC transplantation can be adequately studied in chronic cardiac remodeling using this study set-up and by that provide a translatable murine model facilitating advances in research for new therapeutic approaches to ultimately improve therapy for chronic heart failure.
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), Utrecht, The Netherlands.
Janine C
JC
Deddens
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.|Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Dries A
DA
Feyen
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
Peter-Paul
PP
Zwetsloot
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
Maike A
MA
Brans
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
Sailay
S
Siddiqi
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.|Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Linda W
LW
van Laake
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), Utrecht, The Netherlands.|Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Pieter A
PA
Doevendans
Department of Cardiology, Experimental Cardiology laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), Utrecht, The Netherlands.|Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Joost P
JP
Sluijter
D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000628:therapy*; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*