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(Circulation. 2007;116:I-64 – I-70.)
© 2007 American Heart Association, Inc.

Cell Transplantation and Tissue Regeneration

Prenatally Fabricated Autologous Human Living Heart Valves Based on Amniotic Fluid–Derived Progenitor Cells as Single Cell Source

Dörthe Schmidt, MD, PhD; Josef Achermann, PhD; Bernhard Odermatt, MD; Christian Breymann, MD; Anita Mol, PhD; Michele Genoni, MD; Gregor Zund, MD; Simon P. Hoerstrup, MD, PhD

From the Clinic for Cardiovascular Surgery and Department of Surgical Research (D.S., M.G., G.Z., S.P.H.), University and University Hospital, Zurich, Switzerland; Human Genetics Laboratory (J.A.), Genetica AG, Zurich, Switzerland; Department of Pathology (B.O.), University Hospital, Zurich, Switzerland; GGS (OBGYN Center Seefeld/Hirslanden Clinic Group Zurich) & Feto Maternal Haematology Research Group (C.B.), Obstetric Research, University Hospital Zurich, Switzerland; and the Department of Biomedical Engineering (A.M.), Eindhoven University of Technology, The Netherlands.

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— A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced.

Methods and Results— Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133– and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133– derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133– derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions.

Conclusions— The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.

Key Words: prenatal fetal progenitor cells • tissue engineering • heart valves • amniotic fluid