title: Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.
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.
authors.affiliation: Swiss Center for Regenerative Medicine and Clinic for Cardiovascular Surgery, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Weber
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.forename: Luc
authors.initials: L
authors.lastname: Behr
authors.forename: Roman
authors.initials: R
authors.lastname: Schoenauer
authors.forename: Chad
authors.initials: C
authors.lastname: Brokopp
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Peter
authors.initials: P
authors.lastname: Modregger
authors.forename: Marco
authors.initials: M
authors.lastname: Stampanoni
authors.forename: Divya
authors.initials: D
authors.lastname: Vats
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bürzle
authors.forename: Marc
authors.initials: M
authors.lastname: Farine
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mazza
authors.forename: Thomas
authors.initials: T
authors.lastname: Frauenfelder
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Zannettino
authors.forename: Gregor
authors.initials: G
authors.lastname: Zünd
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretschmar
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D005312:Fetal Blood / Q000166:cytology*; D006351:Heart Valves / Q000166:cytology* / Q000000981:diagnostic imaging; D012756:Sheep / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering; D016216:Ultrasonography, Prenatal
chemical_list: D001672:Biocompatible Materials