Biomedical Engineering Reference
In-Depth Information
will be powerful tools for the effective transplantation of these
differentiated cardiomyocytes.
Challenges to reconstruct pulsatile three-dimensional (3D)
myocardial tissue, having a millimeter-scale thickness, which is
comparable to that of the native human myocardium, have been
already started worldwide. Zimmermann et al. have reconstructed a
synchronously contracting, large-size myocardial tissue (thickness:
1-4 mm; diameter: 15 mm) using neonatal rat cardiac cells and a
mixture of collagen type I/basement membrane protein [25]. The
engineered myocardial tissue contributes to the improvement of
cardiac function in a damaged-heart rat model after transplantation.
Ten-times-repeated in vivo transplantation with triple-layered
beating cardiac cell sheet grafts makes it possible to create a
thicker myocardial tissue, whose thickness is 0.84 ± 0.16 mm, with
well-organized microvessels [49]. The transplanted myocardial
tissue graft beats spontaneously and macroscopically, even after
being resected from the host tissue. Hata et al. have reconstructed
a thicker myocardial tissue (thickness: 800 µm) by combining a
cardiac cell sheet with cardiac cell-seeded decellularized tissue
[50]. On the other hand, various trials to fabricate thicker tissue in
vitro have also started. Because highly cell-dense myocardial tissue
is supported by affluent vasculatures (capillary density: 20 µm),
vascularization/capillary network formation within the tissue is
important for reconstructing a thicker tissue construct in vitro [51].
The cocultivation of endothelial cells (ECs) induces spontaneously
the formations of EC-derived capillary-like networks within cell
sheets and vascular/tubular structures in the 3D tissue constructs
[52-56]. Caspi et al. have reconstructed a synchronously contracting
human cell-derived engineered myocardial tissue construct having
capillary networks [57]. At present, various trials for reconstructing
in vitro a functional, thicker myocardial tissue construct are
performed by various methods, including the usage of bioreactors,
an EC-patterning technique, cultivation under hydrostatic pressure
conditions, the application of mechanical stretch, and the usage of
an oxygen carrier [18, 57-59]. In the near future, the advantages
of various technologies must make possible the fabrication of a
myocardial tissue construct having a thickness comparable to that
of the native myocardium with vascular (vein/artery) networks in
vitro (Fig. 7.1).
