title: Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates.
abstract: OBJECTIVE
  A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates.
  
  
  RESULTS
  Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue.
  
  
  CONCLUSIONS
  Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses.
authors.affiliation: Swiss Center for Regenerative Medicine, Zurich,  Switzerland.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weber
authors.forename: Jacques
authors.initials: J
authors.lastname: Scherman
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.forename: Juerg
authors.initials: J
authors.lastname: Gruenenfelder
authors.forename: Renier
authors.initials: R
authors.lastname: Verbeek
authors.forename: Mona
authors.initials: M
authors.lastname: Bracher
authors.forename: Melanie
authors.initials: M
authors.lastname: Black
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kortsmit
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Roman
authors.initials: R
authors.lastname: Schoenauer
authors.forename: Laura
authors.initials: L
authors.lastname: Baumgartner
authors.forename: Chad
authors.initials: C
authors.lastname: Brokopp
authors.forename: Irina
authors.initials: I
authors.lastname: Agarkova
authors.forename: Petra
authors.initials: P
authors.lastname: Wolint
authors.forename: Gregor
authors.initials: G
authors.lastname: Zund
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
authors.forename: Peter
authors.initials: P
authors.lastname: Zilla
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D005240:Feasibility Studies; D005434:Flow Cytometry; D006085:Graft Survival / Q000502:physiology; D006350:Heart Valve Prosthesis; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000637:transplantation*; D048549:Papio ursinus; D011664:Pulmonary Valve / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D015607:Stents; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous