Biomedical Engineering Reference
In-Depth Information
2001 Orlic et al. suggested that a selected c-kit-positive subpopulation
of HSCs was able to transdifferentiate into cardiomyocytes when
injected into an infarcted heart and generating de novo heart muscle.
More recently, other research groups [27-29] did not confirm this in
vivo data. The positive effect related to the reduction of LV dilatation
and the improvement of LV function upon HSC transplantation,
suggesting a different mechanism than that of neocardiomyocyte
generation.
MSCs are a rare cell population resident in the BM and in the
stroma of other mesenchymal tissues like adipose tissue. These cells
are characterized by self-renewing and multipotency.
MSCs demonstrated good cell plasticity in in vitro experiments,
which confirmed, with promising results, also studies of AMI models
where these cells showed the ability to engraft into the host heart
and differentiate into vascular cells and cardiomyocytes [30, 31]. In
the last years BM mesenchymal and mononuclear cells have been
used in a great number of clinical trials. Lipinski et al. [32] published
in 2007 a review based on the meta-analysis of clinical trials on
intracoronary cell therapy after AMI. They collected and analyzed
data from 10 studies (698 patients, median follow-up 6 months)
and demonstrated that intracoronary cell transplantation following
percutaneous coronary intervention for AMI appears to provide
statistically and clinically relevant benefits on cardiac function and
heart remodeling.
The number of studies performed in chronic models has been
more limited. Liu et al. [33] demonstrated that MSCs transplantation
improved the LVEF, promoted neoangiogenesis, and decreased the
infarct size one month later in a rat model. Similar results were
obtained four weeks after induction of heart failure in rats by Li et
al. [34].
In a large animal model, Waksman et al. [35] transplanted
BM-MNCs in domestic swine. Four weeks later they found an
improvement in angiogenesis and in the reduction of infarct size, but
no clear improvements were found ventricular contractility.
BM-derived cells have been also used in a few clinical trials for
chronic myocardial ischemia. Interesting results were published
in 2009 in
) by
Van Ramshorst et al. [36]. The authors investigated the effect of
intramyocardial BM cell injection on myocardial perfusion and LV
function in patients with chronic myocardial ischemia (50 patients,
Journal of the American Medical Association
(
JAMA
