Biomedical Engineering Reference
In-Depth Information
islands invade the sheet randomly from the host tissue; at day 3,
the sheet reconstructs microvascular networks; and at day 7, well-
organized vascular networks are observed within the transplanted
cell sheet. The result shows that within a few days, the development
of sufficient neovascularization and the rapid vascularization allow
blood to be delivered to the transplanted grafts. A cardiac cell sheet
contains endothelial cells (ECs), and in vitro the cocultivation of ECs
within the cardiac cell sheet induces the expression of angiogenesis-
related genes (vascular endothelial growth factor and Cox-2) and the
formation of an EC-derived capillary-like prevascular network [47].
The prevascular EC networks are closely related to rapid vascular
formation after transplantation [48]. Macroscopic simultaneous
graft beatings are also observed at the earliest period, for example,
three days, after transplantation. Interestingly, the beatings are so
powerful that the electrograms derived from transplanted grafts can
be detected independently from the host heart [49]. Spontaneous
beating continues for up to one year.
6b.3.2
Histological Analyses of Transplanted Cardiac Cell
Sheets
Immunostaining using sarcomeric actinin and Cx43 antibodies
shows well-differentiated sarcomeres in elongated cardiomyocytes
and the diffuse formation of GJs in transplanted myocardial grafts,
respectively [42, 46]. Transmission electron microscopic images
demonstrate well-differentiated myofilaments, typical blood
capillaries, and desmosomes within transplanted myocardial grafts
[15]. Histological analyses show that transplanted layered cardiac
cell sheets are observed to be indistinguishable from real heart
tissues.
6b.3.3
Physiological and Mechanical Analyses of
Myocardial Tissue Grafts after Implantation
After the transplantation of a layered cardiac cell sheet into
subcutaneous tissue, the transplanted tissue graft area significantly
increases in accordance with host growth from 0.63 ± 0.15 cm
2
(
n
=
2
3, mean ± SD, at 1 week after transplantation) to 1.55 ± 0.49 cm
(
n
=
2
3, at 4 weeks) and 1.89 ± 0.22 cm
= 3, at 24 weeks), with the graft
development predominantly in the cephalocaudal direction [46]. The
(
n
