title: Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart disease.
abstract: BACKGROUND
  Cardiomyocytes cultured in a mechanically active 3-dimensional configuration can be used for studies that correlate contractile performance to cellular physiology. Current engineered cardiac tissue (ECT) models use cells derived from either rat or chick hearts. Development of a murine ECT would provide access to many existing models of cardiac disease and open the possibility of performing targeted genetic manipulation with the ability to directly assess contractile and molecular variables.
  
  
  OBJECTIVE
  To generate, characterize, and validate mouse ECT with a physiologically relevant model of hypertrophic cardiomyopathy.
  
  
  RESULTS
  We generated mechanically integrated ECT using isolated neonatal mouse cardiac cells derived from both wild-type and myosin-binding protein C (cMyBP-C)-null mouse hearts. The murine ECTs produced consistent contractile forces that followed the Frank-Starling law and accepted physiological pacing. cMyBP-C-null ECTs showed characteristic acceleration of contraction kinetics. Adenovirus-mediated expression of human cMyBP-C in murine cMyBP-C-null ECT restored contractile properties to levels indistinguishable from those of wild-type ECT. Importantly, the cardiomyocytes used to construct the cMyBP-C(-/-) ECT had yet to undergo the significant hypertrophic remodeling that occurs in vivo. Thus, this murine ECT model reveals a contractile phenotype that is specific to the genetic mutation rather than to secondary remodeling events.
  
  
  CONCLUSIONS
  Data presented here show mouse ECT to be an efficient and cost-effective platform to study the primary effects of genetic manipulation on cardiac contractile function. This model provides a previously unavailable tool to study specific sarcomeric protein mutations in an intact mammalian muscle system.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: de Lange
authors.forename: L F
authors.initials: LF
authors.lastname: Hegge
authors.forename: A C
authors.initials: AC
authors.lastname: Grimes
authors.forename: C W
authors.initials: CW
authors.lastname: Tong
authors.forename: T M
authors.initials: TM
authors.lastname: Brost
authors.forename: R L
authors.initials: RL
authors.lastname: Moss
authors.forename: J C
authors.initials: JC
authors.lastname: Ralphe
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology*; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology*; D023822:Tissue Engineering; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C