Biomedical Engineering Reference
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unpublished data; Seandel et al. 2007 ). The ability of ES-like cells to differentiate
into functional cardiomyocytes exhibiting spontaneous action potentials, as well
as electromechanical coupling between cells, have been confirmed by another
study (Guan et al. 2007 ). Moreover, when undifferentiated ES-like cells were
transplanted directly into the hearts of normal mice they proliferated in the site
of engraftment, gradually lost their pluripotency, and differentiated into vascular
endothelial and smooth muscle cells. Unfortunately, no evidence of differentia-
tion into cardiomyocytes was found (Guan et al. 2007 ). This could be due to the
fact that the ES-like cells were implanted into normal hearts and failed to be
efficiently recruited to the cardiomyocyte fate, as occurs in infarcted hearts
(Singla et al. 2006 ). The generation of cardiomyocytes could also be improved
by pre-differentiating the cells in vitro before transplantation (Zeineddine et al.
2005 ). It is quite interesting that the transplantation of undifferentiated ES-like
cells did not result in tumor formation, since the ability to form teratomas is an
intrinsic property of pluripotent cells (and a key criteria for demonstrating pluri-
potency) (Damjanov and Solter 1974 ; Evans and Kaufman 1981 ; Wobus and
Boheler 2005 ). However, it has been reported previously that intramyocardial
transplantation of undifferentiated ES cells in both mice and rats did not result
in tumor formation either (Singla et al. 2006 ; Min et al. 2002 ). More recently, it
has been found that the formation of teratomas in the heart depends on the num-
ber of undifferentiated ES cell transplanted (Behfar et al. 2007 ).
Using conditions already established for ES cells, germ cell-derived ES-like
cells have been induced towards neural differentiation (Glaser et al. 2008 ). Similar
to ES cells, they formed different kinds of neurons (GABAergic, glutamatergic,
serotonergic, and TH-positive) and glial cells (astrocytes and oligodendrocytes).
During the differentiation process multipotent neural stem cells were formed that
could be propagated as stem cells for many passages and also differentiate into both
neurons and glia. The neurons derived from ES-like cells showed action potentials
and were organized in functional synaptic networks. Interestingly, oligodendro-
cytes derived from ES-like cells were able to home and form myelin in slices of
central nervous system tissue of myelin-deficient rats, suggesting that ES-like cells
could be useful to treat demyelinating disorders (Glaser et al. 2008 ). More recently,
ES-like cells have been differentiated in hepatocytes at a level comparable to ES
cells. However, the amount of hepatocytes generated with the protocols described
from both ES and ES-like cells is still too little to be considered useful in clinical
setting (Loya et al. 2009 ).
The studies above demonstrate that mouse ES-like cells can be differentiated
in vitro using the same protocols already established for mouse ES cells. Although
still very preliminary in this regard, some of these studies tried to evaluate both the
ability of ES-like cells to improve pathological conditions and their safety after
transplantation (Guan et al. 2007 ; Glaser et al. 2008 ). It appears likely that further
studies with the same rationale will support the ability of transplanted ES-like cells
to rescue disease models in a manner comparable to that of ES cells.
In addition, it has also been reported that is possible to correct a genetic defect
in mouse ES-like cells by using a human artificial chromosome (HAC). The delivery
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