Biomedical Engineering Reference
In-Depth Information
spite of material-injection being able to prevent geometry worsening in diseased
hearts, the combination improved cell retention and systolic and diastolic function
more, whereas cell-treatment was only able to ameliorate systolic function.
On the other hand, another aspect involved in the rapid cell clearance is the
immune-rejection that the transplanted cells provoke, being phagocytized by the
inflammatory cells present in the infarcted tissue. In order to avoid this aspect,
another interesting approach is being assayed, which is the encapsulation of the
cells to protect them. Thus, microcapsules allow the diffusion of nutrients and
oxygen towards the cells to keep them alive as well as the cytokines and factors
released by the cells diffuse in the opposite direction, mimicking in this way the
cell paracrine secretion (reviewed in [
250
]). It has been shown for example, that
when hMSCs were encapsulated in RGD-Alginate microbeads and administered in
a model of rat MI, they successfully exerted a paracrine effect, responsible for an
increase of angiogenesis and improvement of cell survival and in last instance, in
the maintenance of LV geometry and preservation of LV function [
251
]. The most
complex challenges of this approach include controlling the growth factor release
rate, the cell survival/replication rate within the capsule and the successful pre-
vention of immune rejection, which hampers its reproducibility [
252
-
255
].
Furthermore, a novel cellular delivery silicon-based platform forming the
''nanoporous micromachined biocapsules'' for cell encapsulation and immuno-
protection is now under investigation, and represents a more recent approach using
non-biodegradable polymers [
256
,
257
].
In general, hydrogel combination or cell microencapsulation are interesting
approaches that have shown good results, although some limitations still need to be
solved, like the fact that they do not assure complete cell retention or adequate distri-
bution of the cells. Techniques like the creation of cell sheets and patches and microt-
issues are now being developed in order to allow, together with greater cell survival, a
more homogeneous, and organized distribution of the cells (reviewed in [
256
]).
5.4.2 Cell Patches
The in vitro construction of 3-D grafts and their epicardial implantation has been
studied by several groups worldwide. In general, this approach provides cells with a
structural support, which helps to increase their retention within the desired area, but
also hinders remodeling processes that eventually end up in chamber dilatation.
The creation of cellular patches has been developed by using different materials
characterized by their biocompatibility and/or biodegradability. Two types of
materials in particular have been tested: porous biomaterials or hydrogel/extra-
cellular matrix (ECM)-based matrices.
Regarding the first ones, for example, Leor and coworkers tested the putative
benefit of treating infarcted rats with a porous 3-D alginate scaffold seeded with rat
CM previously matured in vitro. Nine weeks after transplantation, graft-implanted
animals showed a significant improvement of heart function and decrease in LV
