The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine

•  Introduction •  The evolving definition of the myofibroblast: promoting an understanding of biology and pathology •‐ From early ultrastructural criteria to a comprehensive definition •‐ Immunohistochemistry brings a less precise definition •‐ Consequences of an imprecise definition in normal tissue biology – so‐called myofibroblasts in bladder and gut•  The myofibroblast in fibrotic conditions, tumour stroma and tissue engineering – a therapeutic target in translational medicine •‐ De novo myofibroblastic differentiation and functions of myofibroblasts in granulation tissue, fibroproliferative conditions and tumour stroma •‐ Bone‐marrow‐derived circulating fibrocytes, epithelial‐mesenchymal transformation and the origin of myofibroblasts•  ConclusionsAbstract The phrase ‘translational research’conveys the idea of the pursuit of applications for the treatment of human disease.The myofibroblast, long known for having a role in wound‐healing, and for its presence in fibrotic conditions and tumour stroma, is becoming a focus for translational research, not least through its increasingly documented role as a tumour‐promoting cell.In fibroproliferative conditions, cancer and tissue engineering, the myofibroblast, derived partly and possibly from circulating bone‐marrow‐derived cells and epithelial‐to‐mesenchymal transformation, is attracting great attention.In cancer, this cell was initially regarded as a barrier to tumour dissemination, but there is now a growing body of evidence to indicate that it is an active participant in tumour progression.While the involvement of the myofibroblast in these pathological processes is pushing the myofibroblast into the limelight of translational medicine as a target for potential anti‐fibrotic and anti‐cancer therapy, there are still numerous indications from the literature that the myofibroblast is a poorly understood cell in terms of its differentiation.Partly, this is due to a failure to appreciate the contribution of electron microscopy to understanding the nature of this cell.This paper, therefore, is devoted to detailing the principal phenotypic characteristics of the myofibroblast and promotes the argument that understanding how the myofibroblast carries out its roles in normal biological and in pathological processes will be enhanced by a sound understanding of its cellular differentiation, which in turn arguably demands a significant ultrastructural input.