title: In vivo monitoring of function of autologous engineered pulmonary valve.
abstract: OBJECTIVE
  Clinical translation of tissue-engineered heart valves requires valve competency and lack of stenosis in the short and long term. Early studies of engineered valves showed promise, although lacked complete definition of valve function. Building on prior experiments, we sought to define the in vivo changes in structure and function of autologous engineered pulmonary valved conduits.
  
  
  METHODS
  Mesenchymal stem cells were isolated from neonatal sheep bone marrow and seeded onto a bioresorbable scaffold. After 4 weeks of culture, valved conduits were implanted. Valve function, cusp, and conduit dimensions were evaluated at implantation (echocardiography), at the experimental midpoint (magnetic resonance imaging), and at explant, at 1 day, and 1, 6, 12, or 20 weeks postoperatively (direct measurement, echocardiography). Histologic evaluation was performed.
  
  
  RESULTS
  Nineteen animals underwent autologous tissue-engineered valved conduit replacement. At implantation, valved conduit function was excellent; maximum transvalvular pressure gradient by Doppler echocardiography was 17 mm Hg; most valved conduits showed trivial pulmonary regurgitation. At 6 postoperative weeks, valve cusps appeared less mobile; pulmonary regurgitation was mild to moderate. At 12 weeks or more, valved conduit cusps were increasingly attenuated and regurgitant. Valved conduit diameter remained unchanged over 20 weeks. Dimensional measurements by magnetic resonance imaging correlated with direct measurement at explant.
  
  
  CONCLUSIONS
  We demonstrate autologous engineered tissue valved conduits that function well at implantation, with subsequent monitoring of dimensions and function in real time by magnetic resonance imaging. In vivo valves undergo structural and functional remodeling without stenosis, but with worsening pulmonary regurgitation after 6 weeks. Insights into mechanisms of in vivo remodeling are valuable for future iterations of engineered heart valves.
authors.affiliation: Children's Hospital Boston and Harvard Medical School, Boston, Mass; Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gottlieb
authors.forename: Tandon
authors.initials: T
authors.lastname: Kunal
authors.forename: Sitaram
authors.initials: S
authors.lastname: Emani
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: David W
authors.initials: DW
authors.lastname: Brown
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Powell
authors.forename: Arthur
authors.initials: A
authors.lastname: Nedder
authors.forename: George C
authors.initials: GC
authors.lastname: Engelmayr
authors.forename: Juan M
authors.initials: JM
authors.lastname: Melero-Martin
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sacks
authors.forename: John E
authors.initials: JE
authors.lastname: Mayer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008279:Magnetic Resonance Imaging; D011664:Pulmonary Valve / Q000033:anatomy & histology / Q000601:surgery* / Q000637:transplantation; D012756:Sheep; D023822:Tissue Engineering