MicroRNAs as new maestro conducting the expanding symphony orchestra of regenerative and reparative medicine

Abstract

The human genome encodes 1,048 microRNAs (miRNAs). These miRNAs regulate virtually all biological processes. Leaving ignominy on the significance miRNAs behind we are approaching a new era in tissue repair where an ever expanding orchestra of events that enable tissue repair and regeneration seems to be conducted by miRNAs as the maestro. microRNAs are emerging as molecular rheostats that fine-tune and switch regulatory circuits governing tissue repair. Key elements of tissue repair such as stem cell biology, inflammation, hypoxia-response, and angiogenesis are all under the sophisticated control of a network of specific mRNAs. Embryonic stem cells lacking miRNAs lose their "stemness." Manipulation of specific cellular miRNAs helps enhance reprogramming of somatic cells to an embryonic stem cell-like phenotype helping generate inducible pluripotent stem cells. Expression of miRNAs is subject to control by epigenetic factors. Such control influences the balance between proliferation and differentiation of stem cells. Angiomirs regulate various aspects of angiogenesis, such as proliferation, migration, and morphogenesis of endothelial cells. MiRNAs play a key role in resolution of inflammation. Hypoxia-inducible mRNAs or hypoxamirs suppress mitochondrial respiration, cause cell cycle arrest, and interfere with growth factor signaling. miRNA-210 is a good example in this category that impairs wound closure. As fine tools enabling specific and temporally controlled manipulation of cell-specific miRNAs emerge, miRNA-based therapies hold promise in facilitating tissue repair. Treatment of skin wounds has lower barriers because it lends itself to local delivery of miRNA mimics and antagonizing agents minimizing risks associated with systemic off-target toxicity.