title: Living autologous heart valves engineered from human prenatally harvested progenitors.
abstract: 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.
  
  
  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.
authors.affiliation: Clinic for Cardiovascular Surgery and Department of Surgical Research, University and University Hospital Zurich, Raemistrasse 100, CH 8091 Zurich, Switzerland.
authors.forename: Dörthe
authors.initials: D
authors.lastname: Schmidt
authors.forename: Anita
authors.initials: A
authors.lastname: Mol
authors.forename: Christian
authors.initials: C
authors.lastname: Breymann
authors.forename: Josef
authors.initials: J
authors.lastname: Achermann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Odermatt
authors.forename: Matthias
authors.initials: M
authors.lastname: Gössi
authors.forename: Stefan
authors.initials: S
authors.lastname: Neuenschwander
authors.forename: René
authors.initials: R
authors.lastname: Prêtre
authors.forename: Michele
authors.initials: M
authors.lastname: Genoni
authors.forename: Gregor
authors.initials: G
authors.lastname: Zund
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D020341:Absorbable Implants; D001673:Biodegradation, Environmental; D001705:Bioprosthesis; D019149:Bioreactors; D002469:Cell Separation; D002824:Chorionic Villi; D015193:Chorionic Villi Sampling; D018920:Coculture Techniques; D015925:Cryopreservation; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005838:Genotype; D005865:Gestational Age; D006350:Heart Valve Prosthesis; D006801:Humans; D019520:Living Donors; D008297:Male; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009924:Organ Culture Techniques / Q000379:methods; D010641:Phenotype; D013718:Tensile Strength; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D014021:Tissue Preservation; D020858:Tissue and Organ Harvesting; D014182:Transplantation, Autologous
chemical_list: D004247:DNA