microRNAs (miRNA), non-coding RNA molecules, have emerged as powerful regulators of cellular processes including proliferation, differentiation, and function. Targeting miRNAs allows for cellular reprogramming and is thought to be a promising regenerative therapy for vascular disease states associated with endothelial injury or dysfunction. Researchers at the Brigham sought to understand if differentiating vascular smooth muscle cells into endothelial cells (ECs) using a miRNA cassette would be a promising, novel regenerative strategy for endothelial repair. Using a miRNA cassette composed of miR—142-3p and miR-145-3p inhibitors and miR-146A-5p and miR-181B-5p mimics, researchers created induced endothelial cells (iECs) that exhibited a remarkable similarity to native ECs. Furthermore, in a murine hindlimb ischemia model, the iECs were able to restore blood flow more quickly than conventional ECs. This work contributes to a growing body of evidence supporting the possibility of regenerating endothelial populations from pre-existing mural cells and creating a scalable source of ECs for disease states associated with ischemic injury.
“Collectively, these findings contribute towards an improved understanding of the potential role of miRNAs in cellular differentiation and shows promise as a novel regenerative strategy for endothelial repair,” said senior author Mark W. Feinberg, MD, of the Division of Cardiovascular Medicine. “Through this paper, we show how miRNAs are feasible targets for generating endothelial cells and consider this to be an important step toward miRNA-based treatment of cardiovascular disease.”
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A miRNA cassette reprograms smooth muscle cells into endothelial cells
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Authors declare that they have no competing interests.