title: Low-Intensity Pulsed Ultrasound Improves the Functional Properties of Cardiac Mesoangioblasts.
abstract: Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5'-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of β1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Bernal
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Pérez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: De Lucas
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Nuria San
authors.initials: NS
authors.lastname: Martín
authors.affiliation: Julius Wolff Institute and Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Kadow-Romacker
authors.affiliation: Center for Biomedical Technology, Universidad Politécnica de Madrid, 28223, Pozuelo de Alarcón, Spain.|Departamento de Ciencia de Materiales, ETSI de Caminos, Canales y Puertos, Universidad Politécnica de Madrid, 28040, Madrid, Spain.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Plaza
authors.affiliation: Julius Wolff Institute and Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Raum
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain. b.gonzalez@uem.es.|Universidad Europea (UE), Madrid, Spain. b.gonzalez@uem.es.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Gálvez
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000000981:diagnostic imaging*; D000069453:Ultrasonic Waves; D014463:Ultrasonography
chemical_list: D051785:Smad Proteins; D052004:Bone Morphogenetic Protein Receptors; D001374:Azacitidine
keywords: Cardiac mesoangioblasts; Cytoskeleton; Differentiation; LIPUS; Migration