title: Nitric Oxide Donor Molsidomine Positively Modulates Myogenic Differentiation of Embryonic Endothelial Progenitors.
abstract: Embryonic VE-Cadherin-expressing progenitors (eVE-Cad+), including hemogenic endothelium, have been shown to generate hematopoietic stem cells and a variety of other progenitors, including mesoangioblasts, or MABs. MABs are vessel-associated progenitors with multilineage mesodermal differentiation potential that can physiologically contribute to skeletal muscle development and regeneration, and have been used in an ex vivo cell therapy setting for the treatment of muscular dystrophy. There is currently a therapeutic need for molecules that could improve the efficacy of cell therapy protocols; one such good candidate is nitric oxide. Several studies in animal models of muscle dystrophy have demonstrated that nitric oxide donors provide several beneficial effects, including modulation of the activity of endogenous cell populations involved in muscle repair and the delay of muscle degeneration. Here we used a genetic lineage tracing approach to investigate whether the therapeutic effect of nitric oxide in muscle repair could derive from an improvement in the myogenic differentiation of eVE-Cad+ progenitors during embryogenesis. We show that early in vivo treatment with the nitric oxide donor molsidomine enhances eVE-Cad+ contribution to embryonic and fetal myogenesis, and that this effect could originate from a modulation of the properties of yolk sac hemogenic endothelium.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.|Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tirone
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Conti
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Manenti
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Nicolosi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: D'Orlando
authors.affiliation: MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Azzoni
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Silvia
authors.identifier: http://orcid.org/0000-0003-1753-5346
authors.initials: S
authors.lastname: Brunelli
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055018:Hemangioblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008981:Molsidomine / Q000008:administration & dosage* / Q000494:pharmacology; D024510:Muscle Development / Q000187:drug effects*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy / Q000473:pathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000494:pharmacology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D008981:Molsidomine; D020030:Nitric Oxide Donors; D000099152:Cadherin 5