title: Mesenchymal stem cell transplantation mitigates electrophysiological remodeling in a rat model of myocardial infarction.
abstract: BACKGROUND
  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).
  
  
  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, I(K1), 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).
  
  
  CONCLUSIONS
  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.
authors: The Hull Family Cardiac Fibrillation Management Laboratory, Division of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors: Patrick F H
authors: PF
authors: Lai
authors: Brian K
authors: BK
authors: Panama
authors: Stéphane
authors: S
authors: Massé
authors: Guangming
authors: G
authors: Li
authors: Yaoguang
authors: Y
authors: Zhang
authors: Marjan
authors: M
authors: Kusha
authors: Talha A
authors: TA
authors: Farid
authors: John
authors: J
authors: Asta
authors: Peter H
authors: PH
authors: Backx
authors: Terrence M
authors: TM
authors: Yau
authors: Kumaraswamy
authors: K
authors: Nanthakumar
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D020257:Ventricular Remodeling / Q000502:physiology
keywords: cell transplantation; gene expression; ion channels; mesenchymal stem cells; myocardial infarction; optical mapping