Cicatrización de heridas cutáneas y papel de los miofibroblastos / Cutaneous wound healing and role of myofibroblasts

Objetivo : realizar una revision de las caracteristicas fundamentales de la respuesta de cicatrizacion de heridas (RCH) cutaneas agudas y cronicas. Materiales y Metodos : la informacion se obtuvo de la base de datos pubmed y de los trabajos de inves-tigacion de los autores. Resultados: la RCH cutaneas se desarrolla en cuatro fases secuenciales: hemostasia, inflamacion, proliferacion y remodelacion. Primero ocurre la activacion de fibroblastos, acumulacion de un infiltrado celular inflamatorio que incluye a los miofibroblastos y la alteracion de la matriz extracelular local (MEC). Despues ocurre proliferacion de los miofibroblastos, angiogenesis y proliferacion de las celulas epiteliales. Finalmente tiene lugar el cierre de la herida y el restablecimiento de la arquitectura normal. Las heridas cronicas no siguen el patron normal de reparacion y no ocurre la cicatrizacion. Esto conduce a condiciones patologicas como las ulceras del pie diabetico. Los miofibroblastos desempenan un papel clave y su evolucion coincide con los eventos de la RCH. Primero ocurre la trans-diferenciacion que involucra la conversion de los fibroblastos en reposo a miofibroblastos que proliferan, son fibrogenicos y contractiles. Posteriormente ocurre la perpetuacion del fenotipo activado que incluye respuestas de fibrogenesis, proliferacion, contractibilidad, liberacion de citoquinas proinflamatorias, quimotaxis y degradacion de la MEC. La resolucion involucra la remocion del exceso de MEC y de los miofibroblastos. La eliminacion de estos ocurre por tres mecanismos fundamentales: apoptosis, senescencia y reversion al fenotipo de fibroblastos. Esto constituye un paso fundamental en la restitucion de la integridad del tejido. Conclusiones : se presento una revision actualizada de la RCH fisiologica y patologica.  Palabras clave : cicatrizacion; miofibroblastos; heridas cutaneas; ulcera del pie diabetico. ABSTRACT Objective : provide a review on the main features of both acute and chronic cutaneous wound healing (WHR) and their relationship with myofibroblasts´ functions. Materials and Methods : information was gathered from the pubmed database as well as from author´s publications. Results : cutaneous WHR is a physiological process comprised of four sequential and overlapping stages: hemostasis, inflammation, proliferation and remodelling. Initial stages entail activation of fibroblasts, accumulation of immune cell infiltration including myofibroblasts, and altered local extracellular matrix (ECM). Later stages involve proliferation of myofibroblasts and epithelial cells and angiogenesis. Finally, wound closure and reorganisation of the ECM to an architecture resembling normal tissue occurs. In chronic wounds the normal WHR is stalled leading to static wounds. These are common in pathological conditions such as diabetic foot ulcerations. Myofibroblasts are key players in tissue repair and their evolution is linked to different stages of the wound healing response. Firstly, quiescent fibroblasts transdifferentiate into myofibroblasts that are that proliferating, fibrogenic, and contractile. The following cellular response is called perpetuation of the myofibroblast´s activated phenotype. At this stage, myofibroblasts can develop various responses including fibrogenesis, proliferation, contractility, release of proinflammatory cytokines, chemotaxis and matrix degradation. Finally, the resolution process involves the removal of accumulated ECM and myofibroblasts. Clearance of myofibroblasts can happen through three mechanisms: apoptosis, senescence and reversion to fibroblast´s phenotype. Resolution of myofi-broblast´s activation is an essential step in the restoration of tissue integrity.    Conclusions : we reviewed major characteristics and functions of cutaneous wound healing under physiological conditions or disease. Keywords : healing; myofibroblasts; cutaneous wounds; diabetic foot ulceration.