title: An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure.
abstract: BACKGROUND
  Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF).
  
  
  METHODS
  We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation.
  
  
  RESULTS
  The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure 39%.
  
  
  CONCLUSIONS
  This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center; Department of Physiology. Electronic address: jordan.lancaster@va.gov.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Lancaster
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juneman
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Arnce
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Nicholle M
authors.initials: NM
authors.lastname: Johnson
authors.affiliation: Medical Imaging, University of Arizona, Tucson.
authors.forename: Yexian
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Medical Imaging, University of Arizona, Tucson.
authors.forename: Russell
authors.initials: R
authors.lastname: Witte
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Hoang
authors.initials: H
authors.lastname: Thai
authors.affiliation: Northern Arizona University, Flagstaff.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kellar
authors.affiliation: Department of Physiology.
authors.forename: Jose
authors.initials: J
authors.lastname: Ek Vitorin
authors.affiliation: Department of Physiology.
authors.forename: Janis
authors.initials: J
authors.lastname: Burt
authors.affiliation: Banner Sun Health Research Institute, Sun City, Arizona.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Gaballa
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Bahl
authors.affiliation: Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
authors.forename: Steven
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D006439:Hemodynamics / Q000502:physiology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000637:transplantation*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: cardiomyocytes; cell therapy; chronic heart failure; ejection fraction; ventricles; ventricular function