Biomedical Engineering Reference
In-Depth Information
tissue transplantation is the effective preservation and survival of
the tissue graft into a target tissue after transplantation [14]. It is
generally thought that the therapeutic effects of the transplantation
of autologous cells, including skeletal myoblasts, bone marrow- and
peripheral blood-derived cells, mesenchymal stem cells, cardiac
stem cells, and endothelial progenitor cells, are due to paracrine
effects mediated by cytokines/chemokines produced by these
implanted cells without the direct contribution of their mechanical
assisting effect. On the other hand, the transplantation of pulsatile
myocardial tissue, which can directly contribute to the pulsation of
a damaged heart, must provide a more effective therapy for CVD. In
vitro and in vivo macroscopically pulsatile myocardial tissues can be
reconstructed by using various scaffolds and living cells, or layering
cardiac cell sheets, which are prepared on temperature-responsive
culture dishes [15-23]. The transplantation of these engineered
pulsatile myocardial tissues shows a good therapeutic effect in
various damaged-heart animal models [14, 24, 25]. However, at
present, clinically applicable human cardiomyocytes have been yet
unestablished. Human embryonic stem cells (ESCs) [26] and induced
pluripotent stem cells (iPSCs) [27, 28] are capable of extensive self-
renewal and expansion and have the potential to differentiate into
pulsatile cardiomyocytes [27, 29, 30]. ESCs have some ethical and
moral problems, a risk of immune rejection, and the possibility
of teratoma formation [22, 31]. The establishment of cell banks
containing human ESCs or a technology for transferring somatic cell
nuclei may be able to overcome the limitations [32, 33]. On the other
hand, iPSCs can provide an avenue to solve ethical and moral problems
and a risk of immune rejection. However, the possibility of teratoma
formation yet remains [34]. Although iPSCs have tumorgenicity and
interference of gene expression by the chromosomal integration/
insertion of exogenous genes, these problems are going to be solved
by the untiring efforts of many researchers [35-38]. Further advances
of research studies concerned with (1) effective differentiation from
human ESCs/iPSCs to cardiomyocytes, (2) purification/enrichment
of differentiated cardiomyocytes, (3) removal of undifferentiated
stem cells, etc., are also progressing steadily [39-45]. Human ESC-
derived cardiomyocytes have been used in animal heart disease
models and showed good therapeutic effects [46-48]. In the near
future, ESC-/iPSC-derived cardiomyocytes must be used in clinical
applications. Then, tissue engineering and cell sheet technology
