Differentiation of Mouse Embryonic Fibroblasts (MEFs) into Cardiomyocytes Using Human-Derived Cardiac Inducing RNA (CIR)

Abstract

The present study explores an RNA we have discovered in human heart that induces differentiation of mouse embryonic stem cells and human induced pluripotent stem cells into cardiomyocytes in vitro. We have designated this RNA as Cardiac Inducing RNA or CIR. We now find that CIR also induces mouse embryonic fibroblasts (MEF) to form cardiomyocytes in vitro. For these studies, human-derived CIR is transfected into MEF using lipofectamine. The CIR-transfected mouse fibroblasts exhibit spindle-shaped cells, characteristic of myocardial cells in culture and express cardiac-specific troponin-T and cardiac tropomyosin. As such, the CIR-induced conversion of the fibroblasts into cardiomyocytes in vitro appears to take place without initial dedifferentiation into pluripotent stem cells. Instead, after CIR transfection using a lipofectamine transfection system, over the next 8 days there appears to be a direct transdifferentiation of ˃80% of the cultured fibroblasts into definitive cardiomyocytes. Fewer than ˂7% of the untreated controls using non-active RNA or lipofectamine by itself show cardiomyocyte characteristics. Thus, discovery of CIR may hold significant potential for future use in repair/regeneration of damaged myocardial tissue in humans after myocardial infarction or other disease processes such that affected patients may be able to return to pre-heart-disease activity levels.

LncRNA-CIR6 Mediates Repair of Infarcted Hearts by Inducing MSCs Differentiation into Cardiogenic Cells through CDK1

“…Our hypothesis posits that LncRNA-CIR6 may induce the differentiation of endogenous stem cells in the heart or the injected hUCMSCs into cardiogenic cells. Furthermore, studies have demonstrated that cardiac-inducing RNA-6 (CIR-6) can induce the direct differentiation of murine fibroblasts into cardiomyocytes in vitro [29]. Therefore, we hypothesize that cardiogenic cells not only derive from the differentiation of MSCs induced by LncRNA-CIR6 but may also transform from myocardial fibroblasts under specific conditions.…”

Long Non-Coding RNA-Cardiac-Inducing RNA 6 Mediates Repair of Infarcted Hearts by Inducing Mesenchymal Stem Cell Differentiation into Cardiogenic Cells through Cyclin-Dependent Kinase 1

“…Our hypothesis posits that LncRNA-CIR6 may induce the differentiation of endogenous stem cells in the heart or the injected hUCMSCs into cardiogenic cells. Furthermore, studies have demonstrated that cardiac-inducing RNA 6 (CIR6) can induce the direct differentiation of murine fibroblasts into cardiomyocytes in vitro [ 43 ]. Therefore, we hypothesize that cardiogenic cells not only derive from the differentiation of MSCs induced by LncRNA-CIR6 but may also transform from myocardial fibroblasts under specific conditions.…”