title: Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts.
abstract: OBJECTIVE
  While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation.
  
  
  METHODS
  Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem.
  
  
  RESULTS
  Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm(2). Paravalvular leakage was present in two animals, and central aortic regurgitation due to a single-leaflet prolapse was detected in two, which was primarily related to the leaflet design. No stent dislocation, migration or affection of the mitral valve was observed.
  
  
  CONCLUSIONS
  For the first time, we demonstrate the technical feasibility of a transapical TEHV delivery into the aortic valve position using a commercially available and clinically applied transapical implantation system that allows for exact anatomical positioning. Our data indicate that the combination of TEHV and a state-of-the-art transapical delivery system is feasible, representing an important step towards translational, transcatheter-based TEHV concepts.
authors: Swiss Center for Regenerative Medicine, Zurich, Switzerland.
authors: Maximilian Y
authors: MY
authors: Emmert
authors: Benedikt
authors: B
authors: Weber
authors: Luc
authors: L
authors: Behr
authors: Sebastien
authors: S
authors: Sammut
authors: Thomas
authors: T
authors: Frauenfelder
authors: Petra
authors: P
authors: Wolint
authors: Jacques
authors: J
authors: Scherman
authors: Dominique
authors: D
authors: Bettex
authors: Jürg
authors: J
authors: Grünenfelder
authors: Volkmar
authors: V
authors: Falk
authors: Simon P
authors: SP
authors: Hoerstrup
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000295:instrumentation* / Q000379:methods*; D006351:Heart Valves / Q000601:surgery*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011474:Prosthesis Design; D012756:Sheep; D054457:Tissue Scaffolds
keywords: Aortic valve; Marrow stromal cells; TAVI; Tissue-engineered heart valves; Transapical; Transcatheter