Clinical application of tissue engineered human heart valves using autologous progenitor cells.
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.
Cebotari
Serghei
S
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. cebotari.serghei@mh-hannover.de
Lichtenberg
Artur
A
Tudorache
Igor
I
Hilfiker
Andres
A
Mertsching
Heike
H
Leyh
Rainer
R
Breymann
Thomas
T
Kallenbach
Klaus
K
Maniuc
Liviu
L
Batrinac
Aurel
A
Repin
Oleg
O
Maliga
Oxana
O
Ciubotaru
Anatol
A
Haverich
Axel
A
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