Patrick F.H. Lai and Brian K. Panama share joint first authorship for this manuscript.
Mesenchymal Stem Cell Transplantation Mitigates Electrophysiological Remodeling in a Rat Model of Myocardial Infarction
Article first published online: 3 MAY 2013
© 2013 Wiley Periodicals, Inc.
Journal of Cardiovascular Electrophysiology
Volume 24, Issue 7, pages 813–821, July 2013
How to Cite
LAI, P. F.H., PANAMA, B. K., MASSÉ, S., LI, G., ZHANG, Y., Kusha, M., FARID, T. A., ASTA, J., BACKX, P. H., YAU, T. M. and NANTHAKUMAR, K. (2013), Mesenchymal Stem Cell Transplantation Mitigates Electrophysiological Remodeling in a Rat Model of Myocardial Infarction. Journal of Cardiovascular Electrophysiology, 24: 813–821. doi: 10.1111/jce.12162
Kumaraswamy Nanthakumar and Terrence M. Yau share senior authorship for this manuscript.
This work was funded by the Heart & Stroke Foundation of Ontario (Grant NA#6802). Terrence M. Yau holds the Angelo & Lorenza DeGasperis Chair in Cardiovascular Surgery Research. Brian K. Panama was supported by a fellowship from the Heart and Stroke/Richard Lewar Centre for Excellence. Other authors: No disclosures.
- Issue published online: 1 JUL 2013
- Article first published online: 3 MAY 2013
- Accepted manuscript online: 8 APR 2013 06:05AM EST
- Manuscript Accepted: 12 FEB 2013
- Manuscript Revised: 26 JAN 2013
- Manuscript Received: 7 NOV 2012
- Heart & Stroke Foundation of Ontario. Grant Number: NA#6802
- mesenchymal stem cells;
- cell transplantation;
- myocardial infarction;
- optical mapping;
- ion channels;
- gene expression
Electrophysiological Effects of Mesenchymal Stem Cell Transplantation
Transplantation of mesenchymal stem cells (MSCs) has shown therapeutic potential for cardiovascular diseases, but the electrophysiological implications are not understood. The purpose of this study was to evaluate the impact of MSC transplantation on adverse electrophysiological remodeling in the heart following myocardial infarction (MI).
Methods and Results
Three weeks after coronary ligation to induce MI in rats, MSCs or culture medium were directly injected into each infarct. One to two weeks later, hearts were excised, Langendorff-perfused, and optically mapped using the potentiometric fluorescent dye Di-4-ANEPPS. Quantitative real-time PCR was also performed to assess gene expression. Optical mapping showed that post-MI reduction in conduction velocity (from 0.70 ± 0.04 m/s in 12 normal controls to 0.47 ± 0.02 m/s in 11 infarcted hearts, P < 0.05) was attenuated with MSC transplantation (0.65 ± 0.04 m/s, n = 18, P < 0.05). Electrophysiological changes correlated with higher vascular density and better-preserved ventricular geometry in MSC-transplanted hearts. A number of ion channel genes showed changes in RNA expression following infarction. In particular, the expression of Kir2.1, which mediates the inward rectifier potassium current, IK1, was reduced in infarcted tissues (n = 7) to 13.8 ± 3.7% of normal controls, and this post-MI reduction was attenuated with MSC transplantation (44.4 ± 11.2%, n = 7, P < 0.05).
In addition to promoting angiogenesis and limiting adverse structural remodeling in infarcted hearts, MSC transplantation also alters ion channel expression and mitigates electrophysiological remodeling. Further understanding of the electrophysiological impact of MSC transplantation to the heart may lead to the development of cell-based therapies for post-MI arrhythmias.