Biomedical Engineering Reference
In-Depth Information
thickness of the grafts is also found to increase from 86 ± 5 µm (
n
= 3,
at 1 week) to 94 ± 11 µm (
= 3, at
24 weeks) after transplantation. Although the contractile force of a
one-week tissue graft is too small to be detected, it is found to increase
and measure to be 1.2 ± 0.5 mN (
n
= 3, at 4 weeks) and 104 ± 12 µm (
n
= 3) at
4 weeks and 24 weeks after transplantation, respectively, indicating
that the functional growth of transplanted myocardial tissue grafts
occurs in proportion to host growth. Because cardiomyocytes are
known to rarely divide after birth, increases in both graft volume
and contractile force are believe to be due to the elongation and
hypertrophy of cardiomyocytes [50]. The contractile forces (1.8 mN)
of a transplanted cell sheet construct are found to be larger than
that of in vitro-bioengineered myocardial tissue [39, 46], indicating
that in vivo conditions promote cardiomyocyte hypertrophy. On the
other hand, the contractile forces of in vivo
n
= 3) and 1.8 ± 0.4 mN (
n
layered cell sheet grafts
are smaller than that of neonatal rat whole hearts (approximate
4 mN) [51]. Therefore, in a clinical setting, this contractile force
seems to be insufficient for substituting real heart functions. For
replacing a real heart wall as a future advanced therapy, it is critical
to overcome the size limitation of engineered tissues and to realize
more functional multilayer constructs. Our laboratory makes one
solution for the problems by using the multistep transplantation
of layered cardiac cell sheets and fabricates a strongly pulsatile
myocardial tissue approximately 1 mm in thickness [52]. At present,
various efforts for fabricating thicker tissue in vitro are performed in
many laboratories, including our laboratory.
The conduction velocity of transplanted cell sheet grafts also
increases significantly in a time-dependent manner from 5.9 ± 1.2
cm/s (
-
n
= 3, at 1 week after transplantation) to 13.8 ± 5.4 cm/s
(
= 3, at 24 weeks) [46].
The conduction velocity of the grafts at 24 weeks is faster than
that of in vitro-bioengineered myocardial tissue (approximately
10 cm/s) and are comparable to that of native neonatal rat
ventricles (approximately 20 cm/s) [53]. On the other hand,
the values are relatively small in comparison to native adult rat
ventricles (approximately 30 cm/s). Transplantation period-
dependent acceleration of conduction velocities is consistent with
native heart tissue growth, which demonstrates an increase in its
conduction velocity. The fact that graft growth is correlated with
host development allows layered cardiac cell sheet transplantation
n
= 3, at 4 weeks) and 18.2 ± 3.0 cm/s (
n
