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Theranostics ; 7(19): 4850-4861, 2017.
Article in English | MEDLINE | ID: mdl-29187908

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.


Subject(s)
Adult Stem Cells/transplantation , Cicatrix/metabolism , Interleukin-6/metabolism , Myocardial Infarction/therapy , Adult Stem Cells/metabolism , Aged , Animals , Atrial Appendage/cytology , Cells, Cultured , Female , Fibroblasts/metabolism , Humans , Interleukin-6/genetics , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Middle Aged , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Stem Cell Transplantation
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