title: Clinical application of tissue engineered human heart valves using autologous progenitor cells.
abstract: BACKGROUND
  Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up.
  
  
  RESULTS
  Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients.
  
  
  CONCLUSIONS
  TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. cebotari.serghei@mh-hannover.de
authors.forename: Serghei
authors.initials: S
authors.lastname: Cebotari
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.forename: Igor
authors.initials: I
authors.lastname: Tudorache
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
authors.forename: Heike
authors.initials: H
authors.lastname: Mertsching
authors.forename: Rainer
authors.initials: R
authors.lastname: Leyh
authors.forename: Thomas
authors.initials: T
authors.lastname: Breymann
authors.forename: Klaus
authors.initials: K
authors.lastname: Kallenbach
authors.forename: Liviu
authors.initials: L
authors.lastname: Maniuc
authors.forename: Aurel
authors.initials: A
authors.lastname: Batrinac
authors.forename: Oleg
authors.initials: O
authors.lastname: Repin
authors.forename: Oxana
authors.initials: O
authors.lastname: Maliga
authors.forename: Anatol
authors.initials: A
authors.lastname: Ciubotaru
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000293:Adolescent; D001705:Bioprosthesis; D019149:Bioreactors; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000166:cytology / Q000637:transplantation; D002648:Child; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000637:transplantation*; D011183:Postoperative Complications / Q000209:etiology / Q000601:surgery; D011651:Pulmonary Artery / Q000002:abnormalities; D011664:Pulmonary Valve / Q000002:abnormalities / Q000601:surgery*; D011665:Pulmonary Valve Insufficiency / Q000209:etiology / Q000601:surgery*; D013771:Tetralogy of Fallot / Q000601:surgery; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome