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(Circulation. 2006;114:I-125 – I-131.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Living Autologous Heart Valves Engineered From Human Prenatally Harvested Progenitors

Dörthe Schmidt, MD; Anita Mol, PhD; Christian Breymann, MD; Josef Achermann, PhD; Bernhard Odermatt, MD; Matthias Gössi, PhD; Stefan Neuenschwander, PhD; René Prêtre, MD; Michele Genoni, MD; Gregor Zund, MD; Simon P. Hoerstrup, MD, PhD

From Clinic for Cardiovascular Surgery and Department of Surgical Research (D.S., S.N., R.P., M.G., G.Z., S.P.H.), University and University Hospital, Zurich, Switzerland; Department of Biomedical Engineering (A.M.), Eindhoven University of Technology, the Netherlands; GGS (OBGYN Center Seefeld/Hirslanden Clinic Group Zurich) and Feto Maternal Haematology Research Group (C.B.), Obstetric Research, University Hospital Zurich, Switzerland; Human Genetics Laboratory (J.A.), Genetica, Zurich, Switzerland; Institute for Clinical Pathology (B.O.), University Hospital Zurich, Switzerland; Institute of Polymers (M.G.), Swiss Federal Institute of Technology (ETH), Zurich, Switzerland; Division of Congenital Cardiac Surgery (R.P.), University Children’s Hospital Zurich, Switzerland.

Correspondence to Simon Philipp Hoerstrup, MD, PhD, Clinic for Cardiovascular Surgery and Department of Surgical Research, University and University Hospital Zurich, Raemistrasse 100, CH 8091 Zurich, Switzerland. E-mail: simon_philipp.hoerstrup{at}usz.ch

Background— Heart valve tissue engineering is a promising strategy to overcome the lack of autologous growing replacements, particularly for the repair of congenital malformations. Here, we present a novel concept using human prenatal progenitor cells as new and exclusive cell source to generate autologous implants ready for use at birth.

Methods and Results— Human fetal mesenchymal progenitors were isolated from routinely sampled prenatal chorionic villus specimens and expanded in vitro. A portion was cryopreserved. After phenotyping and genotyping, cells were seeded onto synthetic biodegradable leaflet scaffolds (n=12) and conditioned in a bioreactor. After 21 days, leaflets were endothelialized with umbilical cord blood-derived endothelial progenitor cells and conditioned for additional 7 days. Resulting tissues were analyzed by histology, immunohistochemistry, biochemistry (amounts of extracellular matrix, DNA), mechanical testing, and scanning electron microscopy (SEM) and were compared with native neonatal heart valve leaflets. Fresh and cryopreserved cells showed comparable myofibroblast-like phenotypes. Genotyping confirmed their fetal origin. Neo-tissues exhibited organization, cell phenotypes, extracellular matrix production, and DNA content comparable to their native counterparts. Leaflet surfaces were covered with functional endothelia. SEM showed cellular distribution throughout the polymer and smooth surfaces. Mechanical profiles approximated those of native heart valves.

Conclusions— Prenatal fetal progenitors obtained from routine chorionic villus sampling were successfully used as an exclusive, new cell source for the engineering of living heart valve leaflets. This concept may enable autologous replacements with growth potential ready for use at birth. Combined with the use of cell banking technology, this approach may be applied also for postnatal applications.

Key Words: chorionic villi • endothelial progenitor cells • heart defects (congenital) • heart valves • prenatal progenitor cells • tissue engineering