Biomedical Engineering Reference
In-Depth Information
122
]. Interestingly, it has been demonstrated that the SVF can be isolated and
cultured on methylcellulose dishes, giving rise to vascular and cardiac cells among
others [
123
-
127
]. Studies in vivo with SVF show that this cardiomyogenic cells
can survive and differentiate in rodent acute and chronic myocardial infarction
models, avoiding remodeling and impairment of cardiac function, and promoting
neo-vascularization in the ischemic heart [
128
,
129
].
On the other hand, SVF cells can be cultured in vitro under normal conditions,
deriving toward a much more homogenous population with mesenchymal phe-
notype and features that has been termed as adipose-derived stem cells (ADSC).
Preclinical studies have shown that ADSC not only induce a benefit over cardiac
function, but they can also improve tissue metabolism, vascularization, and infarct
size reduction through a paracrine action [
130
], postulated as their main mecha-
nism of action [
131
,
132
], as their rate of differentiation is quite limited [
131
]. This
has also been related to their in vitro expression of cytokines [
128
,
133
] or to the in
vivo decrease in the level of pro-fibrotic molecules [
134
]. Thus, it has been shown
that ADSC transplantation in a chronic MI model elicited a significant benefit in
cardiac function, which was related to the cell release of growth factors such as
VEGF and HGF [
135
]. Also, in the acute MI (AMI) model, most studies have
shown a consistent and significant benefit of transplanted cells upon cardiac
function (reviewed in [
130
]).
5.3.1.5 Cardiac Progenitor Stem Cells
Despite the traditional dogma regarding the lack of endogenous renewal capacity
of the heart, it has been shown that this organ possesses an intrinsic regenerative
potential, which depends on the presence of cardiac progenitors (CPC) (reviewed
in [
136
]). Importantly, these progenitors, which are localized in small clusters at
the interstitium of the heart, can be isolated, grown, and made to differentiate in
vitro toward mature cardiomyocytes and also, vascular cells. Moreover, an
increase of the CPC pool of the heart has been demonstrated after acute myo-
cardial infarction [
137
] and also, their cardiovascular contribution has been shown
through an improvement of the cardiac function when they are transplanted into
the ischemic heart [
138
].
This adult and autologous population without tumorigenic risk could represent
an ideal source; however, the present description of the cardiac cell populations is
still confusing, since they have been characterized by different markers. Thus, for
example, the first reported cardiac progenitors were defined as a Sca-1
-
cKit
+
population [
138
] whereas almost simultaneously, another study showed the exis-
tence of a Sca-1
+
cKit
-
cell population in the heart [
139
]. Other groups have shown
also the existence of Sca-1
+
CPC populations in the heart [
140
,
141
] some of them
also being defined by the expression of the transporter protein Abcg-2 [
142
]. On
the other hand, the ability of some murine and human heart-derived cells to form
clusters in vitro when cultured in suspension (named ''cardiospheres'') has also
been demonstrated [
143
]. These clusters contain clonally derived cells which
