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(Circulation. 2006;114:I-132 – I-137.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells

Serghei Cebotari, MD; Artur Lichtenberg, MD; Igor Tudorache, MD; Andres Hilfiker, PhD; Heike Mertsching, PhD; Rainer Leyh, MD; Thomas Breymann, MD; Klaus Kallenbach, MD; Liviu Maniuc, MD; Aurel Batrinac, MD; Oleg Repin, MD; Oxana Maliga, MD; Anatol Ciubotaru, MD, PhD; Axel Haverich, MD, PhD

From the Department of Thoracic and Cardiovascular Surgery (S.C., A.L, I.T., A.H., H.M., R.L., T.B., K.K., A.H.), Hannover Medical School, Germany; Scientific and Practical Center of Cardiovascular Surgery (L.M., A.B., O.R., O.M., A.C.), Chisinau, Moldova.

Correspondence to Serghei Cebotari, Hannover Medical School, Department of Thoracic and Cardiovascular Surgery, Carl-Neuberg-Straße 1, D-30625 Hannover, Germany. E-mail cebotari.serghei{at}mh-hannover.de

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.

Methods and 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.

Key Words: congenital • heart defects • surgery • valves