Fig 1.
The concept of a subpulmonary „neo-ventricle”from engineered heart tissue.
A: Extracardiac tunnel for the treatment of children with univentricular hearts. Commonly, a non-contractile GoreTex-conduit is used to bypass blood from the inferior caval vein to the right pulmonary artery. B: Our group aims for a contractile, valved conduit made from engineered heart tissue (EHT) to propel blood actively through the lungs and avoid endorgan damage in the long-term.
Fig 2.
Generation of a simple contractile conduit from EHT.
The illustration shows the construction of a simple „neo-ventricle”out of engineered heart tissue. Two lamellar EHTs were wrapped around the right SVC of adult Wistar rats. The ends were sutured using a single stitch of nylon suture.
Fig 3.
Hematoxylin and eosin (HE) staining of “neo-ventricle” 56 days after implantation around the superior caval vein (SVC) of rats.
A: Engineered heart tissue organized around the SVC. Thick bundles of cross-striated cardiomycytes are shown above the smooth muscle of the native vessel wall. The arrow indicates a suture with surrounding lymphocytic infiltration. B: Magnification of detail in left panel. Cross-striation can be seen in the highly organized cardiomyocytes within the contractile conduit. The arrow indicates red blood cells in a capillary. Scale bar: 50 μm.
Fig 4.
Cardiac morphology of EHT-conduit 28 days after grafting.
A+D: Connexin 43 (red), an important gap junction protein indicating functional syncytium of the grafted cells is shown. Scale bar: 20 μm. B+E: CD31 staining (green) revealed dense vascularization. Vessels displayed a small diameter compatible with capillaries. Alpha-actin staining (red) showed dense bundles of cross-striated cardiomyocytes around the SVC. C+F: DAPI (blue) labeling of cells before implantation allowed for clear identification of grafted cells after harvest of the specimen. Scale bar: 50 μm. G: Overview of depicted (A-F) sarcomeric details showing the circumferential alignment of the „neo-ventricle“. Scale bar: 100 μm.
Fig 5.
Sarcomeric integrity of implanted EHTs after 14 and 28 days in vivo.
A+B: Cross-striation of cardiomyocytes in DAPI-positive areas is shown. Scale bar: 20 μm.
Fig 6.
Cine MRI 14 days after implantation of EHTs around the SVC of rats.
A: Approximately 1 mm above the right atrium two stripes of EHT were implanted around the SVC (box). No stenosis or constriction of the vein could be detected in the treatment group. B: The box shows the SVC of a Sham operated animal 14 days after the procedure. Scale bars: 1 cm.