Biomedical Engineering Reference
In-Depth Information
RNA (reviewed in [
89
]). With respect to the use of these cells in cellular therapy,
Nelson et al. [
167
] reported that the intramyocardial delivery of mouse iPS cells
also achieved the in situ regeneration of cardiac tissue, while also improving the
post-ischemic cardiac function . Other groups demonstrated that iPS cells can
derive into spontaneously contracting cardiomyocytes [
168
,
169
]. However, other
results showed that iPS-derived cardiomyocytes have impaired capacity to form
differentiated, functional cells [
170
], and also that iPS cells, like ESC, can form
tumors [
92
]. To overcome this problem, the field needs to develop methods to
enrich iPS cells derivatives for cardiomyocytes or other useful cell types (such as
endothelial, smooth muscle and stromal cells), with strict methods for sorting out
the remaining undifferentiated cells, like the use of fluorescent molecules (cDy1)
that stain pluripotent cells in live conditions [
171
]. In any case, further work will
be required to define more precisely the safety, phenotype and maturation potential
of cardiomyocytes derived from iPS cells [
89
].
To sum up, the injection of many of the cell types described above seems to
improve cardiac function in animal models of MI, suggesting that the simple short-
term improvement in cardiac function cannot be taken as direct evidence of car-
diac regeneration per se. Moreover, a portion of the effect may relate to effects of
decreasing wall stress by increasing the tissue mass in a thinning myocardial wall,
an anatomic effect that is independent of a real regenerative effect (reviewed in
[
172
]). Up to now, results suggest that the benefit induced by stem cells in the
treated hearts is due to paracrine mechanisms more than through cardiovascular
differentiation of the transplanted cells, despite the reported ability of some adult
stem cell populations to in vivo differentiate to the cardiovascular lineages (mainly
to the vascular lineages) (reviewed in [
173
]). This hypothesis has been reinforced
by the fact that injection of conditioned media recovered from cultured stem cells
can also provoke a benefit in the injected hearts [
174
,
175
] (See Fig.
5.2
).
5.3.2 Clinical Assays
Although more basic studies are needed in order to better understand the mech-
anisms involved in cardiac repair, a number of early phase clinical as well as
randomized trials have been performed to determine the feasibility and safety of
stem cell transplantation. Also, several ongoing Phase III trials have now been
initiated (reviewed in [
176
]) for efficacy testing. Based on the encouraging
experimental results and due to their putative feasibility and safety, skeletal
myoblasts and bone marrow derived stem cells have been the first populations
tested (reviewed in [
98
]). Their autologous application (that avoids the need for
immune-suppression), and innocuous tissue isolation and relatively easy cell
culture procedure when needed, have been important factors taken into account for
their choice. More recently, ADSC and CSC have also been introduced in the
clinical arena (see Table
5.3
).
