Abstract
The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response.
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Abbreviations
- MI:
-
Myocardial infarction
- MSC:
-
Mesenchymal stem cell
- XFM:
-
X-ray fused to MRI
- IV:
-
Intravenous
- TE:
-
Transendocardial
- LAD:
-
Left anterior descending
- MRI:
-
Magnetic resonance imaging
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Acknowledgments
The authors would like to thank Craig Schneider and Medtronic, Minneapolis, MN for providing Reveal XT implanted loop recorders and assisting with device interrogation. Many thanks also to Peter Altman and Biocardia Inc. (San Carlos, CA) for making Helix catheters/Morph catheters available to us for pre-clinical studies.
Funding
This work was supported by the NIH/NHLBI Production Assistant for Cellular Therapies (PACT) contract number HHSN268201000010C. Statistical consultation support was provided by National Institutes of Health grant UL1TR000427 to the University of Wisconsin Institute of Clinical Translational Research from the National Center for Advancing Translational Sciences (NCATS).
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Associate Editor Angela Taylor oversaw the review of this article
Clinical Relevance Statement
There is evidence to suggest that single dose administration of bone marrow-derived mesenchymal stem cells for the treatment of myocardial infarction offers short-term benefit. In clinical practice, serial dosing may be required; however, this has not been tested in pre-clinical models. Our data suggest that a biologically plausible and clinically practical delivery approach of intravenous followed by transendocardial catheter delivery of bone marrow-derived mesenchymal stem cells improves contractile reserve and suppresses ventricular arrhythmias.
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Schmuck, E.G., Koch, J.M., Hacker, T.A. et al. Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction. J. of Cardiovasc. Trans. Res. 8, 438–448 (2015). https://doi.org/10.1007/s12265-015-9654-0
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DOI: https://doi.org/10.1007/s12265-015-9654-0