Living autologous heart valves engineered from human prenatally harvested progenitors.
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.
Schmidt
Dörthe
D
Clinic for Cardiovascular Surgery and Department of Surgical Research, University and University Hospital Zurich, Raemistrasse 100, CH 8091 Zurich, Switzerland.
Mol
Anita
A
Breymann
Christian
C
Achermann
Josef
J
Odermatt
Bernhard
B
Gössi
Matthias
M
Neuenschwander
Stefan
S
Prêtre
René
R
Genoni
Michele
M
Zund
Gregor
G
Hoerstrup
Simon P
SP
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
D004247:DNA