Theranostics 2017; 7(19):4850-4861. doi:10.7150/thno.19435

Research Paper

Interleukin-6 Mediates Post-Infarct Repair by Cardiac Explant-Derived Stem Cells

Audrey E Mayfield1, Pushpinder Kanda1, Alex Nantsios1, Sandrine Parent1, Seth Mount1, Somya Dixit1, Bin Ye1, Richard Seymour1, Duncan J Stewart2, Darryl R Davis1✉

1. University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, Canada K1Y4W7;
2. Ottawa Hospital Research Institute, Division of Regenerative Medicine, Department of Medicine, University of Ottawa, Ottawa, Canada K1H8L6

Abstract

Although patient-sourced cardiac explant-derived stem cells (EDCs) provide an exogenous source of new cardiomyocytes post-myocardial infarction, poor long-term engraftment indicates that the benefits seen in clinical trials are likely paracrine-mediated. Of the numerous cytokines produced by EDCs, interleukin-6 (IL-6) is the most abundant; however, its role in cardiac repair is uncertain. In this study, a custom short-hairpin oligonucleotide lentivirus was used to knockdown IL-6 in human EDCs, revealing an unexpected pro-healing role for the cytokine.

Methods: EDCs were cultured from atrial appendages donated by patients undergoing clinically indicated cardiac surgery. The effects of lentiviral mediated knockdown of IL-6 was evaluated using in vitro and in vivo models of myocardial ischemia.

Results: Silencing IL-6 in EDCs abrogated much of the benefits conferred by cell transplantation and revealed that IL-6 prompts cardiac fibroblasts and macrophages to reduce myocardial scarring while increasing the generation of new cardiomyocytes and recruitment of blood stem cells.

Conclusions: This study suggests that IL-6 plays a pivotal role in EDC-mediated cardiac repair and may provide a means of increasing cell-mediated repair of ischemic myocardium.

Keywords: Cell therapy, interleukin-6, stem cells, myocardial infarction

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How to cite this article:
Mayfield AE, Kanda P, Nantsios A, Parent S, Mount S, Dixit S, Ye B, Seymour R, Stewart DJ, Davis DR. Interleukin-6 Mediates Post-Infarct Repair by Cardiac Explant-Derived Stem Cells. Theranostics 2017; 7(19):4850-4861. doi:10.7150/thno.19435. Available from http://www.thno.org/v07p4850.htm