Biomedical Engineering Reference
In-Depth Information
3.6
Problems and Answers
From the first case of cell transplantation into a human heart in 2000
great improvements have been made, many clinical trials started,
and thousands of people involved; nevertheless, many questions are
still without a clear answer.
The main problem of heart cell transplantation based on direct
cell injection is the low homing and retention of cells into the
damage area. In fact, irrespective of cell types and delivery systems
cell survival upon injection and engraftment into the heart is very
low. Zhang et al. [54] in 2001 showed that more than 90% of injected
cardiomyocytes disappeared within one week after administration
and one half of the cells were lost on the first day. These results have
been observed similarly by Menasche et al. [55] with the injection of
SKMs and Toma et al. [56] with BM-derived cells (less than 0.5% of
live cells after 4 days). More recently, Freyman et al. [57] compared
three different cell delivery systems in a pig infarction model and
found that the percentage of engrafted cells, two weeks after BM-
derived cell transplantation, was low irrespective of the types
of delivery systems used (6% by intracoronary infusion, 3% by
intramyocardial injection, and no cells by intravenous injection).
To clarify the mechanisms involved in cell engraftment scientists
must consider both the stem cell pool injected and the injured
myocardium, and in fact, both counterparts play a key role in the
success of heart tissue regeneration and heart function restoration.
It is well known that the event cascade which follows AMI is
characterized by the activation of pro-inflammatory cells. These
cells in turn recruit other cells related to the immune system, which
contribute to the following events of neosynthesis of the ECM
by activated fibroblasts, leading to the generation of scar fibers,
which dramatically impair the architecture of cardiac muscle and
its function. The high levels of pro-inflammatory cytokines and
free radicals provide a harmful environment for injection cells and
strongly contribute to the quick disappearance of cells and the
related low engraftment. In a different way, patients suffering from
chronic ischemia, where oxygen and nutrients are supplied at a low
level, apoptosis and chronic inflammation are strongly active. In
recent years, researchers have attempted to increase cell survival
and engraftment rates in different ways.
Focusing on the heart, researchers have used different approaches
attempting to change in a more suitable environment cell viability
and engraftment using various methods based on preconditioning.
To achieve this goal, researchers used different methods like, for
