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In the early 1990's our team developed and patented one of the first percutaneous heart valve systems working with Dr. Ivan Casagrande and Dr. Domingos Moraes in Brazil. We learned in this experience that a patient is nearly always better off keeping their own heart valve it they can. The aim of

La regeneración cardíaca requiere una cascada compleja de acontecimientos con numerosos factores, la mayoría aún no clarificados, que limitan la terapia celular y su traslación a la práctica clínica. Las células tienen que injertarse, sobrevivir e integrarse funcionalmente en el órgano para restaurar su función. De la misma manera que en los tejidos originales, un sistema complejo de señales bien definidas, muchas de ellas generadas desde la matriz extracelular, son necesarias para desarrollar una fisiología celular normal. El planteamiento de combinar conocimientos de biología celular e ingeniería con materiales biocompatibles para restaurar tejidos biológicos y mejorar su función es el fundamento de la ingeniería tisular que define un nuevo abordaje de la regeneración cardíaca.La investigación y desarrollo de un miocardio bioartificial tiene gran interés clínico. La estrategia es el uso de biomateriales para desarrollar una microatmósfera que proporcione a las células endógenas y exógenas un ambiente óptimo para la reparación de tejidos. Los conocimientos adquiridos en el desarrollo de biomateriales aportan las bases para desarrollar matrices 3D que ofrecen el ambiente idóneo para la liberación de células y genes que dirijan las células terapéuticas hacia el fenotipo funcional. La descelularización de órganos para construir nuevas matrices es un nuevo concepto de investigación, desarrollado gracias al desarrollo de nanomateriales que aseguran un nicho celular apropiado para la diferenciación celular y la terapia génica o farmacológica.Cardiac regeneration requires a complex cascade of events. There are many factors, most of them still no clarified, that limit the effectiveness of the stem cell therapy and their translation to the clinic. Cells should graft, survive and functionally integrate to the target organ in order to have a chance to restore its function. As in original tissues, a complex and well defined set of signals, many of them coming from the extracellular matrix, is required for normal cell physiology. The idea of combining principles from cell biology and engineering of biocompatible materials in order to create biologic replacement structures that restore, maintain, or improve tissue function, is at the basis of the tissue engineering and defines a different approach to the cardiac regeneration.Research and development of bioartificial myocardium is of great clinical interest. The rationale for the use of specific biomaterials is to allow the creation of a microatmosphere where the exogenous and endogenous cells find the microenvironment optimal for repair. Biomaterials science gives us important tools to build this extracellular matrix. Functionalized 3D systems can provide the correct environment and act as a delivery system for cells and genes, guiding the therapeutic cells to the functional phenotype. Organ decellularization for bioscaffolds fabrication is a new investigated concept. nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/ administration properties.

Follistatin (FST) and the related proteins FSTL1 and FSTL3 are crucial modulators of the transforming growth factor (TGF)-beta superfamily and function by neutralizing activins, a group of proteins implicated in many biologic processes, such as cell proliferation and differentiation, immune responses, various endocrine activities, wound repair, inflammation and fibrosis. Activins are increased in the serum of heart failure patients and in cardiomyocytes after experimental myocardial infarction, suggesting the involvement of activins in heart failure pathogenesis. FST is considered to be a key modulator in muscle development, differentiation and regeneration, and it has been implicated in the repair of mesodermal- and endodermal-derived tissues, promoting cell proliferation and hampering fibrogenesis. We have previously demonstrated that electrostimulation (ES) induces cardiomyocyte pre-commitment of both stem and non-stem cells in vitro. In this study, we evaluated whether applying ES to human mesenchymal stromal cells (hMSC) modulated FST production.hMSC were electrostimulated with 10 and 40 V for 12 h. FST production was assessed by immunostaining, Western blot and flow cytometry.FST was up-regulated in hMSC after ES and was associated with cardiomyogenic differentiation of hMSC by short-term ES.The possibility of stimulating the production of FST, a key regulator of mesodermal differentiation, in adult stem cells, while avoiding the drawbacks of conditioned media, dangerous drugs and gene delivery, has relevant potential therapeutic clinical applications. Additionally, this simple differentiation system could be useful for elucidating the molecular mechanisms driving the stem cell-differentiation process.