Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation

Benedikt Weber, Maximilian Y. Emmert, Luc Behr, Roman Schoenauer, Chad Brokopp, Cord Drögemüller, Peter Modregger, Marco Stampanoni, Divya Vats, Markus Rudin, Wilfried Bürzle, Marc Farine, Edoardo Mazza, Thomas Frauenfelder, Andrew C. Zannettino, Gregor Zünd, Oliver Kretschmar, Volkmar Falk, Simon P. Hoerstrup

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.

Original languageEnglish
Pages (from-to)4031-4043
Number of pages13
JournalBiomaterials
Volume33
Issue number16
DOIs
Publication statusPublished or Issued - Jun 2012

Keywords

  • Amniotic fluid stem cells
  • Composite matrix
  • Fetal model
  • Heart valve
  • Prenatal intervention
  • Tissue engineering

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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