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. Methods and 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 (nϭ12) 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

Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues

“…The cells result in considerable improvements to ventricular function, capillary density and scar tissue (Ventura et al 2007) and similar findings have been reported using native rat AMSCs (Fujimoto et al 2009). Stem cells derived from prenatal chorionic villi were also successfully engineered into a living autologous heart valve, which could have postnatal applications for repairing congenital cardiac malformations (Schmidt et al 2006).…”

Tissue engineering on matrix: future of autologous tissue replacement

“…1). Several different cell sources serve as the basis for the generation of these constructs, where minimally invasively accessible stem and progenitor cells have shown tremendous potential [7][8][9].…”

“…A new concept, using human prenatal progenitor cells derived from chorionic villi and umbilical cord blood for the production of autologous heart valve leaflets, has been introduced by Schmidt et al [9]. Furthermore, human amniotic fluid-derived cells, as an easily accessible cell source, have been used as a sole cell source for the fabrication of living autologous heart valves prior to birth [8,41].…”

“…When the matrix material is from homogenic origin, the limited availability of donor valves and associated ethical concerns represent a considerable shortcoming. Moreover, the lack of evidence of growth and remodeling capacities of valve replacements when using decellularized scaffolds seems to be a further drawback, especially with regard to the pediatric field [9]. These drawbacks and uncertainties raise a common concern associated with the use of decellularized starter matrices, also fuelling the search for synthetic scaffold alternatives.…”

Adipose Derived Tissue Engineered Heart Valve

“…A major focus in heart valve tissue engineering is the in vitro creation of mature tissue structures compliant with native valve functionality. Various cell types have been investigated for their suitability for heart valve tissue engineering including high remodeling capacity of the Extracellular Matrix (ECM), including prenatal cells [11][12][13], umbilical cord [14][15][16] and vascular derived cells [17][18][19]. Furthermore the observed multipotency of adult Mesenchymal Stem Cells (MSCs) including their ability to differentiate into cells found in the adult heart, such as cardiomyocytes and endothelial cells, sparked interest to develop them for future cell-based therapy such as heart valve engineering.…”