title: Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero.
abstract: Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg(-/-) mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg(-/-) foetal hearts. CPCs harvested from Speg(-/-) mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg(-/-) mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg(-/-) mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.|Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Sean R R
authors.initials: SRR
authors.lastname: Hall
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Ghanta
authors.affiliation: Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.|Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Moises
authors.initials: M
authors.lastname: Di Sante
authors.affiliation: Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.|Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.affiliation: Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.|Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.|Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Perrella
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000196:embryology / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D005315:Fetal Diseases / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D046128:Fetal Therapies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology; D014599:Uterus
chemical_list: D009124:Muscle Proteins; C484400:Speg protein, mouse; D009219:Myosin-Light-Chain Kinase