Biomedical Engineering Reference
In-Depth Information
2a.4
Mesenchymal Stem Cells
Mesenchymal stem cells are stromal cells in mesenchymal tissues,
such as bone marrow and adipose tissues, and generally have
the potential to differentiate into adipocytes, osteocytes, and
cartilaginous cells. Several studies have demonstrated in vitro
differentiation of mesenchymal stem cells into cardiomyocytes,
prompting high expectations for the differentiation of these cells
into the cardiomyocyte lineage after transplantation. However,
similar to other cells tested, while transplanted mesenchymal stem
cells did ameliorate cardiac dysfunction accompanied by increased
neovascularization and suppression of fibrosis in models of acute and
chronic myocardial infarct and dilated cardiomyopathy [12-14], only
a very small proportion of transplanted cells actually differentiated
into cardiomyocytes [15, 16]. Gnecchi et al. reported that the
supernatants of bone marrow-derived mesenchymal stem cell
culture, maintained under hypoxic conditions, suppressed hypoxia-
induced myocardial cell death in vitro and that this suppressive effect
was enhanced when a similarly conditioned medium recovered from
the culture of mesenchymal stem cells overexpressing Akt was used
[17]. The effects of this conditioned medium were also confirmed
in a model of myocardial infarction, suggesting the involvement
of paracrine effects in the mechanism for improvement of cardiac
function after transplantation of mesenchymal stem cells [18]. In
fact, the expression levels of VEGF, FGF-2, HGF, IGF-1, and thymosinβ4
were up-regulated in bone marrow-derived mesenchymal stem
cells exposed to hypoxic stimulation and in those overexpressing
Akt [18]. Comprehensive gene expression analysis, performed by
the same research group, showed that up-regulation of sFRP2 was
most noticeable in mesenchymal stem cells overexpressing Akt and
that the medium of mesenchymal stem cells overexpressing Akt lost
its ability to reduce infarction injury size when cells were treated
with short interfering ribonucleic acid (siRNA) against sFRP2 [19].
Taken together, transplantation of mesenchymal stem cells appears
to have direct cardioprotective and angiogenic effects by using
secreted proteins as mediators. On the other hand, paracrine effects
characteristic of mesenchymal stem cells include suppression of
fibrosis and anti-inflammatory actions. The suppression of fibrosis
by mesenchymal stem cell transplantation has been reported
in other organs, including lung [20], liver [21], and kidney [22].
